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1.
Aubert M Pomeranz LE Blaho JA 《Apoptosis : an international journal on programmed cell death》2007,12(1):19-35
Expression of HSV-1 genes leads to the induction of apoptosis in human epithelial HEp-2 cells but the subsequent synthesis
of infected cell protein prevents the process from killing the cells. Thus, viruses unable to produce appropriate prevention
factors are apoptotic. We now report that the addition of either a pancaspase inhibitor or caspase-9-specific inhibitor prevented
cells infected with an apoptotic HSV-1 virus from undergoing cell death. This result indicated that HSV-1-dependent apoptosis
proceeds through the mitochondrial apoptotic pathway. However, the pancaspase inhibitor did not prevent the release of cytochrome
c from mitochondria, implying that caspase activation is not required for this induction of cytochrome c release by HSV-1. The release of cytochrome c was first detected at 9 hpi while caspase-9, caspase-3 and PARP processing were detected at 12 hpi. Finally, Bax accumulated
at mitochondria during apoptotic, but not wild type HSV-1 infection. Together, these findings indicate that HSV-1 blocks apoptosis
by precluding mitochondrial cytochrome c release in a caspase-independent manner and suggest Bax as a target in infected human epithelial cells. 相似文献
2.
Chien-Li Chiu Jen-Leih Wu Guor-Mour Her Yi-Li Chou Jiann-Ruey Hong 《Apoptosis : an international journal on programmed cell death》2010,15(6):653-668
Aquatic birnavirus induces post-apoptotic necrotic cell death via a newly synthesized protein-dependent pathway. However,
the involvement of viral genome-encoded protein(s) in this death process remains unknown. In the present study, we demonstrated
that the submajor capsid protein, VP3, up-regulates the pro-apoptotic protein, Bad, in fish and mouse cells. Western blot
analysis revealed that VP3 was expressed in CHSE-214 cells at 4 h post-infection (pi), indicating an early role during viral replication. We cloned
the VP3 gene and tested its function in fish and mouse cells; VP3 overexpression induced apoptotic cell death by TUNEL assay. In
addition, it up-regulated Bad gene expression in zebrafish ZLE cells by threefold at 12 h post-transfection (pt) and in mouse NIH3T3 cells by tenfold at
24 h pt. VP3 up-regulation of Bad expression altered mitochondria function, inducing mitochondrial membrane potential (MMP)
loss and activating initiator caspase-9 and effector caspase-3. Furthermore, reduced Bad expression (65% reduction), MMP loss
(up to 40%), and enhanced cell viability (up to 60%) upon expression of VP3 antisense RNA in CHSE-214 cells at 24 h post-IPNV
infection was observed. Finally, overexpression of the anti-apoptotic gene, zfBcl-xL, reduced VP3-induced apoptotic cell death and caspase-3 activation at 24 h in fish cells. Taken together, these results suggest
that aquatic birnavirus VP3 induces apoptosis via up-regulation of Bad expression and mitochondrial disruption, which activates a downstream caspase-3-mediated death pathway that is blocked by
zfBcl-xL. 相似文献
3.
Gastric irritant-induced apoptosis in guinea pig gastric mucosal cells in primary culture 总被引:3,自引:0,他引:3
Tsutsumi S Tomisato W Takano T Rokutan K Tsuchiya T Mizushima T 《Biochimica et biophysica acta》2002,1589(2):168-180
When the gastric mucosa is exposed to various irritants, apoptosis and subsequent gastric mucosal lesion can result in vivo. We here show that gastric irritants induced apoptosis in gastric mucosal cells in primary culture and examined its molecular mechanism. Ethanol, hydrogen peroxide, and hydrochloric acid all induced, in a dose-dependent manner, cell death, apoptotic DNA fragmentation, and chromatin condensation, suggesting that each of these gastric irritants induced apoptosis in vitro. Since each of these irritants decreased the mitochondrial membrane potential and stimulated the release of cytochrome c from mitochondria, gastric irritant-induced apoptosis seems to be mediated by mitochondrial dysfunction. Caspase-3, caspase-8, and caspase-9-like activities were all activated simultaneously by each of these irritants and the activation was concomitantly with cell death and apoptotic DNA fragmentation. Furthermore, pre-treatment of gastric mucosal cells with an inhibitor of caspase-8 suppressed the onset of cell death as well as the stimulation of caspase-3- and caspase-9-like activities caused by each of these gastric irritants. Based on these results, we consider that caspase-8, an initiator caspase, plays an important role in gastric irritant-induced apoptosis. 相似文献
4.
Rapid cold-hardening protects <Emphasis Type="Italic">Drosophila melanogaster</Emphasis> from cold-induced apoptosis 总被引:1,自引:0,他引:1
Yi SX Moore CW Lee RE 《Apoptosis : an international journal on programmed cell death》2007,12(7):1183-1193
The rapid cold-hardening (RCH) response increases the cold tolerance of insects by protecting against non-freezing, cold-shock
injury. Apoptosis, or programmed cell death, plays important roles in development and the elimination of sub-lethally damaged
cells. Our objectives were to determine whether apoptosis plays a role in cold-shock injury and, if so, whether the RCH response
protects against cold-induced apoptosis in Drosophila melanogaster. The present study confirmed that RCH increased the cold tolerance of the adults at the organismal level. No flies in the
cold-shocked group survived direct exposure to ‒7°C for 2 h, whereas significantly more flies in the RCH group survived exposure
to ‒7°C for 2 h after a 2-h exposure to 5°C. We used a TUNEL assay to detect and quantify apoptotic cell death in five groups
of flies including control, cold-shocked, RCH, heat-shocked (37.5°C, 30 min), and frozen (‒20°C, 24 h) and found that apoptosis
was induced by cold shock, heat shock, and freezing. The RCH treatment significantly improved cell viability by 38% compared
to the cold-shocked group. Cold shock-induced DNA fragmentation shown by electrophoresis provided further evidence for apoptosis.
SDS-PAGE analysis revealed an RCH-specific protein band with molecular mass of ∼150 kDa. Western-blotting revealed three proteins
that play key roles in the apoptotic pathway: caspase-9-like (apoptotic initiator), caspase-3-like (apoptotic executioner)
and Bcl-2 (anti-apoptotic protein). Consequently, the results of this study support the hypothesis that the RCH response protects
against cold-shock-induced apoptosis. 相似文献
5.
Oropesa M de la Mata M Maraver JG Cordero MD Cotán D Rodríguez-Hernández A Domínguez-Moñino I de Miguel M Navas P Sánchez-Alcázar JA 《Apoptosis : an international journal on programmed cell death》2011,16(4):404-424
Microtubule cytoskeleton is reformed during apoptosis, forming a cortical structure beneath plasma membrane, which plays an
important role in preserving cell morphology and plasma membrane integrity. However, the maintenance of the apoptotic microtubule
network (AMN) during apoptosis is not understood. In the present study, we examined apoptosis induced by camptothecin (CPT),
a topoisomerase I inhibitor, in human H460 and porcine LLCPK-1α cells. We demonstrate that AMN was organized in apoptotic
cells with high ATP levels and hyperpolarized mitochondria and, on the contrary, was dismantled in apoptotic cells with low
ATP levels and mitochondrial depolarization. AMN disorganization after mitochondrial depolarization was associated with increased
plasma membrane permeability assessed by enhancing LDH release and increased intracellular calcium levels. Living cell imaging
monitoring of both, microtubule dynamics and mitochondrial membrane potential, showed that AMN persists during apoptosis coinciding
with cycles of mitochondrial hyperpolarization. Eventually, AMN was disorganized when mitochondria suffered a large depolarization
and cell underwent secondary necrosis. AMN stabilization by taxol prevented LDH release and calcium influx even though mitochondria
were depolarized, suggesting that AMN is essential for plasma membrane integrity. Furthermore, high ATP levels and mitochondria
polarization collapse after oligomycin treatment in apoptotic cells suggest that ATP synthase works in “reverse” mode during
apoptosis. These data provide new explanations for the role of AMN and mitochondria during apoptosis. 相似文献
6.
Tretiakova I Blaesius D Maxia L Wesselborg S Schulze-Osthoff K Cinatl J Michaelis M Werz O 《Apoptosis : an international journal on programmed cell death》2008,13(1):119-131
Myrtucommulone (MC) is a unique, nonprenylated acylphloroglucinol contained in the leaves of myrtle (Myrtus communis). Here, we addressed the potential of MC to induce apoptosis of cancer cells. MC potently induced cell death of different
cancer cell lines (EC50 3–8 μM) with characteristics of apoptosis, visualized by the activation of caspase-3, -8 and -9, cleavage of poly(ADP-ribose)polymerase
(PARP), release of nucleosomes into the cytosol, and DNA fragmentation. MC was much less cytotoxic for non-transformed human
peripheral blood mononuclear cells (PBMC) or foreskin fibroblasts (EC50 cell death = 20–50 μM), and MC up to 30 μM hardly caused processing of PARP, caspase-3, -8 and -9 in human PBMC. MC-induced
apoptosis was mediated by the intrinsic rather than the extrinsic death pathway. Thus, MC caused loss of the mitochondrial
membrane potential in MM6 cells and evoked release of cytochrome c from mitochondria. Interestingly, Jurkat cells deficient
in caspase-9 were resistant to MC-induced cell death and no processing of PARP or caspase-8 was evident. In cell lines deficient
in either CD95 (Fas, APO-1) signalling, FADD or caspase-8, MC was still able to potently induce cell death and PARP cleavage.
Conclusively, MC induces apoptosis in cancer cell lines, with marginal cytotoxicity for non-transformed cells, via the mitochondrial
cytochrome c/Apaf-1/caspase-9 pathway.
I. Tretiakova and D. Blaesius contributed equally to this work. 相似文献
7.
Li YC Lin HJ Yang JH Yang JS Ho HC Chang SJ Hsai TC Lu HF Huang AC Chung JG 《Neurochemical research》2009,34(3):418-429
Studies were designed to investigate the effects of baicalein on mouse–rat hybrid retina ganglion cells (N18) to better understand
its effect on apoptosis and apoptosis-related genes in vitro. Cell viability, reactive oxygen species (ROS), cytoplasmic Ca2+, mitochondrial membrane potential (MMP), apoptosis induction, and caspases-3 activity were examined by flow cytometric assay.
Apoptosis-associated proteins such as p53, Bax, Bcl-2, cytochrome c, and caspase-3 were examined by Western blot. We demonstrated the increase in the levels of p53, Bax, and cytochrome c and decrease in the level of Bcl-2, which are associated with the induction of apoptotic cell death after 24 h treatment
with baicalein in N18 cells. Baicalein induced an increase in the cytoplasmic levels of ROS and Ca2+ in 1 h and reached their peak at 3 h, and thereafter a loss of MMP by flow cytometry. We also demonstrated a release of the
cytochrome c from mitochondria into cytosol and an activation of caspase-3, which led to the occurrence of apoptosis in N18 cells treated
with baicalein by Western blot. Pretreatment was conducted with BAPTA (intracellular calcium chelator) in baicalein-treated
cells, the decline of MMP was recovered, and the increase in the level of cytoplasmic Ca2+ was suppressed, and the proportion of apoptosis was also markedly diminished. In conclusion, our data suggests that oxidative
stress and cellular Ca2+ modulates the baicalein-induced cell death via a Ca2+-dependent mitochondrial death pathway in N18 cells. 相似文献
8.
Kaiyu Liu Qinghua Tang Cong Fu Jianxin Peng Hong Yang Yi Li Huazhu Hong 《Cytotechnology》2007,54(2):97-105
The relation between autophagy and apoptosis has not been clearly elucidated. Here, we reported that apoptosis followed autophagy
in insect Spodoptera litura cells (Sl) undergoing glucose starvation. Sl cells have been adapted to Leibovitz-15 medium supplemented with glucose (1.0 g/l)
and 5% fetal bovine serum (FBS), used for mammalian cell cultures. If glucose (1 g/l) or glutamine (1.6 g/l) had not been
supplemented in L-15 medium with 5% FBS, Sl cells began to form many vacuoles and these vacuoles gradually enlarged in the
cytoplasm, which were autophagic vacuoles. However, these large vacuoles began to disappear gradually after 48 h of glucose
starvation, accompanied with remarkable apoptosis without apoptotic bodies, which was demonstrated by DNA fragmentation and
activation of caspase-3-like. During glucose starvation, Sl cell ATP concentrations gradually decreased. Interestingly, if
the conditioned L-15 medium without glucose was replaced with fresh L-15 medium supplemented with glucose or glutamine after
the cultures had been starved seriously for 48 h or longer, the formation of apoptotic bodies was initiated. These data suggested
that the partial depletion of cell ATP triggered apoptosis following autophagy in glucose-starved Sl cells and the formation
of apoptotic bodies required higher level of ATP than DNA fragmentation and activation of caspase-3-like activity. Additionally,
the disappearance of autophagic vacuoles, negative staining of neutral red, green staining of acridine orange and diffusion
of acid phosphatase activity in Sl cells at the late stage of starvation (over 48 h) suggested that the dysfunction of lysosome
was more likely to involve in apoptosis. The facts that Actinomycin D-induced apoptosis was partially inhibited and cyclosporin
A, blocking the opening of mitochondrial permeability transition (MPT) pores, inhibited partially apoptosis in glucose-starved
Sl cells, suggested the pathway of glucose starvation-induced apoptosis seemed to be different from that induced by actinomycin
D and the opening of MPT pores on mitochondria probably involved in apoptosis triggered by glucose starvation, respectively. 相似文献
9.
Photodynamic therapy-induced death of HCT 116 cells: Apoptosis with or without Bax expression 总被引:2,自引:0,他引:2
Chiu SM Xue LY Azizuddin K Oleinick NL 《Apoptosis : an international journal on programmed cell death》2005,10(6):1357-1368
Cell death following photodynamic therapy (PDT) with the photosensitizer Pc 4 involves the intrinsic pathway of apoptosis.
To evaluate the importance of Bax in apoptosis after PDT, we compared the PDT responses of Bax-proficient (Bax+/−) and Bax knock-out (BaxKO) HCT116 human colon cancer cells. PDT induced a slow apoptotic process in HCT Bax+/− cells following a long delay in the activation of Bax and release of cytochrome c from mitochondria. Although cytochrome c was not released from mitochondria following PDT in BaxKO cells, an alternative mechanism of caspase-dependent apoptosis
with extensive chromatin and DNA degradation was found in these cells. This alternative process was less efficient and slower
than the normal apoptotic process observed in Bax+/− cells. Early events upon PDT, such as the loss of mitochondrial membrane potential, photodamage to Bcl-2, and activation
of p38 MAP kinase, were observed in both HCT116 cell lines. In spite of differences in the efficiency and mode of apoptosis
induced by PDT in the Bax+/− and BaxKO cells, they were found to be equally sensitive to killing by PDT, as determined by loss of clonogenicity. Thus,
for Pc 4-PDT, the commitment to cell death occurs prior to and independent of Bax activation, but the process of cellular
disassembly differs in Bax-expressing vs. non-expressing cells. 相似文献
10.
The Role of Ca2+ on the DADS-induced Apoptosis in Mouse–Rat Hybrid Retina Ganglion Cells (N18) 总被引:2,自引:0,他引:2
Diallyl disulfide (DADS), a component of garlic, has been shown to induce growth inhibition and apoptosis in human cancer cell types. The present studies were designed to investigate the effects of DADS on mouse–rat hybrid retina ganglion cells (N18) to better understand its effect on apoptosis and apoptosis-related genes in vitro. Cell viability, cell cycle analysis, reactive oxygen species (ROS), Ca2+ production, mitochondria membrane potential, apoptosis induction, associated gene expression and caspases-3 activity were examined by flow cytometric assay and/or Western blot. After 24-h treatment with DADS, a dose- and time-dependent decrease in the viability of N18 cells was observed and the approximate IC50 was 27.6 μM. The decreased percentage of viable cells are associated with the production of ROS then followed by the production of Ca2+ which is induced by DADS. DADS induced apoptosis in N18 cells via the activation of caspase-3. DADS increased the protein levels of p53, cytochrome c and phosphated JNK within 24 h of treatment and it decreased the levels of Bcl-2 and those factors may have led to the mitochondria depolarization of N18 cells. DADS induced apoptosis were accompanied by increased levels of Ca2+ and decreased mitochondrial membrane potential which then led to release the cytochrome c, cleavage of pro-caspase-3. Deleted levels of Ca2+ by BAPTA-AM 10 μM (intracellular calcium chelator) then led to decrease DADS-induced apoptosis. Inhibition of caspase-3 activation by inhibitor (z-VAD-fmk) completely blocked DADS-induced apoptosis on N18 cells. The results indicated that oxidative stress modulates cell proliferation and Ca2+ modulates the cell death induced by DADS. 相似文献
11.
An endoplasmic reticulum-specific stress-activated caspase (caspase-12) is implicated in the apoptosis of A549 epithelial cells by respiratory syncytial virus 总被引:20,自引:0,他引:20
Respiratory syncytial virus (RSV) infection induced programmed cell death or apoptosis in the cultured lung epithelial cell line, A549. The apoptotic cells underwent multiple changes, including fragmentation and degradation of genomic DNA, consistent with the activation of the DNA fragmentation factor or caspase-activated DNase (DFF or CAD). The infection led to activation of FasL; however, a transdominant mutant of FAS-downstream death domain protein, FADD, did not inhibit apoptosis. Similarly, modest activation of cytoplasmic apoptotic caspases, caspase-3 and -8, were observed; however, only a specific inhibitor of caspases-3 inhibited apoptosis, while an inhibitor of caspase-8 had little effect. No activation of caspase-9 and -10, indicators of the mitochondrial apoptotic pathway, was observed. In contrast, RSV infection strongly activated caspase-12, an endoplasmic reticulum (ER) stress response caspase. Activation of the ER stress response was further evidenced by upregulation of ER chaperones BiP and calnexin. Antisense-mediated inhibition of caspase-12 inhibited apoptosis. Inhibitors of NF-kappa B had no effect on apoptosis. Thus, RSV-induced apoptosis appears to occur through an ER stress response that activates caspase-12, and is uncoupled from NF-kappa B activation. 相似文献
12.
Calcium ion is essential for cellular functions including signal transduction. Uncontrolled calcium stress has been linked
causally to a variety of neurodegenerative diseases. Thapsigargin, which inhibits Ca2+-ATPase in the endoplasmic reticulum (ER) and blocks the sequestration of calcium by the ER, induced apoptotic cell death
(chromatin condensation and nuclear fragmentation) accompanied by GRP78 protein expression and caspase-3 activation in rat
fetal cortical neurons (days in vitro 9–10). Blockade of N-methyl-d-aspartate (NMDA) receptors with NMDA antagonists induced apoptosis without GRP78 protein expression. Apoptosis accompanied
both caspase-9 and caspase-3 activation. We then examined whether GSK-3 is involved in thapsigargin-induced cell death by
using GSK-3 inhibitors. We assayed the effects of selective GSK-3 inhibitors, SB216763, alsterpaullone and 1-azakenpaullone,
on thapsigargin-induced apoptosis. These inhibitors completely protected cells from thapsigargin-induced apoptosis. In addition,
GSK-3 inhibitors inhibited caspase-9 and caspase-3 activation accompanied by thapsigargin-induced apoptosis. These results
suggest that thapsigargin induces caspase-dependent apoptosis mediated through GSK-3β activation in rat cortical neurons. 相似文献
13.
Singapore grouper iridovirus,a large DNA virus,induces nonapoptotic cell death by a cell type dependent fashion and evokes ERK signaling 总被引:2,自引:0,他引:2
Huang X Huang Y Ouyang Z Xu L Yan Y Cui H Han X Qin Q 《Apoptosis : an international journal on programmed cell death》2011,16(8):831-845
Virus induced cell death, including apoptosis and nonapoptotic cell death, plays a critical role in the pathogenesis of viral
diseases. Singapore grouper iridovirus (SGIV), a novel iridovirus of genus Ranavirus, causes high mortality and heavy economic losses in grouper aquaculture. Here, using fluorescence microscopy, electron microscopy
and biochemical assays, we found that SGIV infection in host (grouper spleen, EAGS) cells evoked nonapoptotic programmed cell
death (PCD), characterized by appearance of cytoplasmic vacuoles and distended endoplasmic reticulum, in the absence of DNA
fragmentation, apoptotic bodies and caspase activation. In contrast, SGIV induced typical apoptosis in non-host (fathead minnow,
FHM) cells, as evidenced by caspase activation and DNA fragmentation, suggesting that SGIV infection induced nonapoptotic
cell death by a cell type dependent fashion. Furthermore, viral replication was essential for SGIV induced nonapoptotic cell
death, but not for apoptosis. Notably, the disruption of mitochondrial transmembrane potential (ΔΨm) and externalization of
phosphatidylserine (PS) were not detected in EAGS cells but in FHM cells after SGIV infection. Moreover, the extracellular
signal-regulated kinase (ERK) signaling was involved in SGIV infection induced nonapoptotic cell death and viral replication.
This is a first demonstration of ERK-mediated nonapoptotic cell death induced by a DNA virus. These findings contribute to
understanding the mechanisms of iridovirus pathogenesis. 相似文献
14.
Nottrott S Schoentaube J Genth H Just I Gerhard R 《Apoptosis : an international journal on programmed cell death》2007,12(8):1443-1453
Clostridium difficile toxin A (TcdA) is one of two homologous glucosyltransferases that mono-glucosylate Rho GTPases. HT29 cells were challenged
with wild-type and mutant TcdA to investigate the mechanism by which apoptosis is induced. The TcdA-induced re-organization
of the actin cytoskeleton led to an increased number of cells within the G2/M phase. Depolymerization of the actin filaments
with subsequent G2/M arrest, however, was not causative for apoptosis, as shown in a comparative study using latrunculin B.
The activation of caspase-3, -8, and -9 strictly depended on the glucosylation of Rho GTPases. Apoptosis measured by flow
cytometry was completely abolished by a pan-caspase inhibitor (z-VAD-fmk). Interestingly, cleavage of procaspase-3 and Bid
was not inhibited by z-VAD-fmk, but was inhibited by the calpain/cathepsin inhibitor ALLM. Cleavage of procaspase-8 was susceptible
to inhibition by z-VAD-fmk and to the caspase-3 inhibitor Ac-DMQD-CHO, indicating a contribution to the activation of caspase-3
in an amplifying manner. Although TcdA induced mitochondrial damage and cytochrome c release, p53 was not activated or up-regulated. A p53-independent apoptotic effect was also checked by treatment of HCT 116
p53−/− cells. In summary, TcdA-induced apoptosis in HT29 cells depends on glucosylation of Rho GTPases leading to activation of
cathepsins and caspase-3. 相似文献
15.
Programmed cell death (PCD), now known as apoptosis, is accompanied by specific morphological features. In this study, fusaric acid, a fusarium mycotoxin, was used to examine cell death in saffron (Crocus sativus Linnaeus) roots, using several apoptosis assays. Our results show that moderate FA doses (50–100 μM) induce apoptotic features while high FA doses (> 200 μM) stimulate necrosis. The apoptotic-like features induced by moderate doses of FA include chromatin condensation, formation of condensed chromatin spheres which bud from the nucleus, fragmentation of nucleosomal DNA into ∼ 180 bp fragments, exposure of phosphatidyl serine to the external membrane leaflet, delivery of cytochrome c to cytosol, and generation of H2O2. These apoptotic alterations in root cells are not observed in the presence of serine protease, caspase-1 or caspase-3 inhibitors. It is proposed that production of H2O2 and release of cytochrome c into the cytosol may activate caspase-like proteases and thus establish the apoptotic pathway. As nuclei budding spheres formed in plant root cells after exposure to 50–100 μM FA doses seem to be digested inside the cytosol, we suggest labeling them as internal apoptotic bodies (IAB) that may be more informative than previously used term, apoptotic-like bodies.Electronic Supplementary Material Supplementary material is available to authorised users in the online version of this article at . 相似文献
16.
Martin-Latil S Mousson L Autret A Colbère-Garapin F Blondel B 《Journal of virology》2007,81(9):4457-4464
Rotaviruses are the leading cause of infantile viral gastroenteritis worldwide. Mature enterocytes of the small intestine infected by rotavirus undergo apoptosis, and their replacement by less differentiated dividing cells probably leads to defective absorptive function of the intestinal epithelium, which, in turn, contributes to osmotic diarrhea and rotavirus pathogenesis. Here we show that infection of MA104 cells by the simian rhesus rotavirus strain RRV induced caspase-3 activation, DNA fragmentation, and cleavage of poly(ADP-ribose) polymerase; all three phenomena are features of apoptosis. RRV induced the release of cytochrome c from mitochondria to the cytosol, indicating that the mitochondrial apoptotic pathway was activated. RRV infection of MA104 cells activated Bax, a proapoptotic member of the Bcl-2 family, as revealed by its conformational change. Most importantly, Bax-specific small interfering RNAs partially inhibited cytochrome c release in RRV-infected cells. Thus, mitochondrial dysfunction induced by rotavirus is Bax dependent. Apoptosis presumably leads to impaired intestinal functions, so our findings contribute to improving our understanding of rotavirus pathogenesis at the cellular level. 相似文献
17.
Lin CF Chen CL Chang WT Jan MS Hsu LJ Wu RH Tang MJ Chang WC Lin YS 《The Journal of biological chemistry》2004,279(39):40755-40761
Recently, caspase-2 was shown to act upstream of mitochondria in stress-induced apoptosis. Activation of caspase-8, a key event in death receptor-mediated apoptosis, also has been demonstrated in death receptor-independent apoptosis. The regulation of these initiator caspases, which trigger the mitochondrial apoptotic pathway, is unclear. Here we report a potential regulatory role of caspase-2 on caspase-8 during ceramide-induced apoptosis. Our results demonstrate the sequential events of initiator caspase-2 and caspase-8 activation, Bid cleavage and translocation, and mitochondrial damage followed by downstream caspase-9 and -3 activation and cell apoptosis after ceramide induction in T cell lines. The expression of truncated Bid (tBid) and the reduction in mitochondrial transmembrane potential were blocked by caspase-2 or caspase-8, but not caspase-3, knockdown using an RNA interference technique. Ceramide-induced caspase-8 activation, mitochondrial damage, and apoptosis were blocked in caspase-2 short interfering RNA-expressing cells. Therefore, caspase-2 acts upstream of caspase-8 during ceramide-induced mitochondrial apoptosis. Similarly, sequential caspase-2 and caspase-8 activation upstream of mitochondria was also observed in etoposide-induced apoptosis. These data suggest sequential initiator caspase-2 and caspase-8 activation in the mitochondrial apoptotic pathway induced by ceramide or etoposide. 相似文献
18.
Sujit K. Bhutia 《Cell biology international》2009,33(7):720-727
In our previous study, Abrus abrin derived peptide fraction (ABP) with molecular weight in range of 600-1500 Da was shown to have potent antitumor activity in Dalton's lymphoma (DL) tumor bearing mice. The purpose of this study was to elucidate the mechanism of mitochondrial apoptosis induced by the peptide fraction. ABP was found to have selective antiproliferative activity (10 ng-100 ng/ml) on several tumor cell lines in vitro without having any cytotoxic effect on normal cell lines with a dose of 1000 ng/ml. Analysis of the growth inhibitory mechanism in HeLa cells revealed DNA fragmentation with appearance of the sub G0/G1 peak indicative of apoptosis. Further investigation results showed that the apoptotic machinery of HeLa induced by ABP was associated with the release of reactive oxygen species, a drop in mitochondrial transmembrane potential, upregulation of Bax, downregulation of Bcl-2, and activation of caspase-3. The peptide fraction was found to target mitochondria of HeLa cells as observed by confocal microscopy. This peptide fraction offers a source of mitochondria penetrating peptides which might have therapeutic induction of apoptosis in cancer cells. 相似文献
19.
Antiproliferative activity of sulfated polysaccharide isolated from an enzymatic digest of Ecklonia cava on the U-937 cell line 总被引:1,自引:0,他引:1
Yasantha Athukorala Gin Nae Ahn Young-Heun Jee Gi-Young Kim Soo-Hyun Kim Jin-Hwan Ha Jung-Sook Kang Ki-Wan Lee You-Jin Jeon 《Journal of applied phycology》2009,21(3):307-314
A sulfated polysaccharide purified from a brown alga Ecklonia cava, having high anticoagulant activity was investigated for its antiproliferative effect on murine colon carcinoma (CT-26),
human leukemic monocyte lymphoma (U-937), human promyelocytic leukemia (HL-60), and mouse melanoma (B-16) cell lines. The
sulfated polysaccharide isolated and purified from an enzymatic extract of E. cava had a good selective tumor cell growth inhibition effect; its effect on HL-60 and U-937 was especially promising. The IC50 value for the sulfated polysaccharide from E. cava (ECSP) on U-937 was 43.9 μg mL−1. The presence of the sample in the cell culture media stimulated the induction of apoptosis, revealed by nuclear staining
with Hoechst 33342. The apoptosis induction was confirmed by the cell cycle analysis, while pronounced sub-G1 phase arrests
of 9.5% and 13.8% were also clearly observed when the cells were treated at 15 and 30 μg mL−1 of ECSP in the U-937 cell line, respectively. After a 24-h incubation period, ECSP dose-dependently enhanced the DNA fragmentation
on the U-937 cell line as observed in the agarose gel electrophoresis assay. To rule out the action mechanism of ECSP for
its anticancer activity, some western blot analyses were conducted with several antibodies (caspase-7, caspase-8, Bax, Bcl-xL,
and PARP) and ECSP had a clear effect on the caspase -7 and 8 which cleave protein substrates, including PARP, an inducer
of apoptosis responsible for DNA cleavage. Moreover, ECSP controlled the cellular transmembrane molecules like Bax and Bcl-xL.
Taken together, the above results demonstrate that the apoptosis for antiproliferative effect of ECSP was clearly induced
on U-937 cells. 相似文献
20.
Lasfer M Vadrot N Aoudjehane L Conti F Bringuier AF Feldmann G Reyl-Desmars F 《Cell biology and toxicology》2008,24(1):55-62
The heavy metal cadmium, an environmental pollutant, has been widely demonstrated to be toxic, in particular for liver. In
murines, cadmium induces apoptosis of hepatocytes and hepatomas. In human cells, apoptosis induced by cadmium has been exclusively
demonstrated in tumoral cell lines. Nothing was known in normal liver, in vitro or in vivo. In the present study, we examined the effects of cadmium in nonmalignant human hepatocytes. For that purpose, we investigated
whether cadmium was able to induce apoptosis of normal human hepatocytes (NHH) in primary culture and of a SV40-immortalized
human hepatocyte (IHH) cell line. Treatment of IHH and NHH with cadmium induced the presence of a sub-G1 population at 10 and 100 μmol/L, respectively. DAPI staining of both cell types treated with cadmium 100 μmol/L revealed
the induction of nuclear apoptotic bodies, supporting the hypothesis of apoptosis. In IHH and NHH, cadmium 100 μmol/L induced
PARP cleavage into a 85 kDa fragment. In order to investigate the involvement of mitochondria in cadmium-induced apoptosis,
we measured the mitochondrial membrane potential (ΔΨm). We observed that in IHH and NHH, cadmium 100 μmol/L induced a decrease of ΔΨm. As expected, cadmium under the same conditions enhanced caspase-9 and caspase-3 activities. In addition, cadmium from 1
to 100 μmol/L induced the expression of p53 and phosphorylation of its Ser15 in IHH and NHH. In conclusion, we showed in this
study that human hepatocytes were sensitive to cadmium and apoptosis induced at concentrations suggested in the literature
to inhibit p53 DNA-binding and DNA repair. 相似文献