共查询到20条相似文献,搜索用时 31 毫秒
1.
Serhan Ozyıldırım Abdulkerim Kasim Baltaci Engin Sahna Rasim Mogulkoc 《Biological trace element research》2017,176(1):64-64
A ginseng polysaccharide was extracted, purified, and modified by nitric acid-selenious acid (HNO3-H2SeO3) method to yield one selenylation-modified polysaccharide (sGP). We reported for the first time the anticancer potential of sGP on the human promyelocytic leukemia HL-60 cell line and evaluated its relevant underlying mechanism. Our results showed that sGP markedly inhibited the growth of HL-60 cells via induction of apoptosis. The event of apoptosis was accompanied by the formation of apoptotic bodies; the release of cytochrome c; loss of mitochondrial membrane potential; and activation of caspase-9, caspase-3, and cleavage of poly ADP ribose polymerase (PARP) in HL-60 cells. In addition, western blot analysis showed that sGP inhibited antiapoptotic Bcl-2 protein expression and increased proapoptotic Bax protein expression in cells under identical conditions. Together, our study suggests that sGP induces apoptosis of HL-60 cells through the mitochondrial-dependent pathway. 相似文献
2.
Qiao S Murakami K Zhao Q Wang B Seo H Yamashita H Li X Iwamoto T Ichihara M Yoshino M 《Neurochemical research》2012,37(2):417-427
Growth-inhibitory effects of mimosine, a plant amino acid, on rat C6 glioma cells were analyzed. Mimosine markedly inhibited
proliferation and induced apoptosis of C6 glioma cells in a dose- and time-dependent manner. Mimosine-mediated apoptosis was
accompanied by promoting reactive oxygen species (ROS) generation in mitochondria, and by decreased mitochondrial membrane
potential (Δψ), and release of cytochrome c from mitochondria, followed by caspase 3 activation. Furthermore, mimosine increased the phosphorylation level of c-Jun-N-terminal
protein kinase and p38, which was the downstream effect of ROS accumulation. Mimosine was confirmed to show profound effects
on apoptosis of C6 glioma cells by ROS-regulated mitochondria pathway, and these results bear on the hypothesized potential
for mimosine as promising agents in the treatment of malignant gliomas. 相似文献
3.
Liu GY Liao YF Hsu PC Chang WH Hsieh MC Lin CY Hour TC Kao MC Tsay GJ Hung HC 《Apoptosis : an international journal on programmed cell death》2006,11(10):1773-1788
Antizymes delicately regulate ornithine decarboxylase (ODC) enzyme activity and polyamine transportation. One member of the
family, antizyme-1, plays vital roles in molecular and cellular functions, including developmental regulation, cell cycle,
proliferation, cell death, differentiation and tumorigenesis. However, the question of how does it participate in the cell
apoptotic mechanism is still unsolved. To elucidate the contribution of human antizyme-1 in haematopoietic cell death, we
examine whether inducible overexpression of antizyme enhances apoptotic cell death. Antizyme reduced the viability in a dose-
and time-dependent manner of human leukemia HL-60 cells, acute T leukemia Jurkat cells and mouse macrophage RAW 264.7 cells.
The apoptosis-inducing activities were determined by nuclear condensation, DNA fragmentation, sub-G1 appearance, loss of mitochondrial membrane potential (Δψ
m
), release of mitochondrial cytochrome c into cytoplasm and proteolytic activation of caspase 9 and 3. Following conditional antizyme overexpression, all protein
levels of cyclin-dependent kinases (Cdks) and cyclins are not significantly reduced, except cyclin D, before their entrance
into apoptotic cell death. However, introduced cyclin D1 into Jurkat T tetracycline (Tet)-On cell system still couldn’t rescue
cells from apoptosis. Antizyme doesn’t influence the expression of tumor suppressor p53 and its downstream p21, but it interferes
in the expressions of Bcl-2 family. Inducible antizyme largely enters mitochondria resulting in cytochrome c release from mitochondria to cytosol following Bcl-xL decrease and Bax increase. According to these data, we suggest that
antizyme induces apoptosis mainly through mitochondria-mediated and cell cycle-independent pathway. Furthermore, antizyme
induces apoptosis not only by Bax accumulation reducing the function of the Bcl-2 family, destroying the Δψ
m
, and releasing cytochrome c to cytoplasm but also by the activation of apoptosomal caspase cascade. 相似文献
4.
Polimeno Lorenzo Pesetti Barbara Lisowsky Thomas Iannone Florenzo Resta Leonardo Giorgio Floriana 《Free radical research》2013,47(9):865-875
Background: Hydrogen peroxide, as other reactive oxygen species (ROS) produced during redox processes, induces lipid membrane peroxidation and protein degeneration causing cell apoptosis. ROS are recently considered as messengers in cell signalling processes, which, through reversible protein disulphide bridges formation, activate regulatory factors of cell proliferation and apoptosis. Disulphide bridges formation is catalysed by sulphydryl oxidase enzymes.Aim: The neuroprotective effect of ALR protein (Alrp), a sulphydryl oxidase enzyme, on H2O2-induced apoptosis in SH-SY5Y cells has been evaluated.Methods: Cell viability, flow cytometric evaluation of apoptotic cells, fluorescent changes of nuclear morphology, immunocytochemistry Alrp detection, Western blot evaluation of mitochondrial cyt c release and mitochondrial swelling were determined.Results: Alrp prevents the H2O2-induced cell viability loss, apoptotic cell death and mitochondrial swelling in SH-SY5Y cells in culture.Conclusions: The data demonstrate that Alrp improves SH-SY5Y cells survival in H2O2-induced apoptosis. It is speculated that this effect could be related to the Alrp enzymatic activity. 相似文献
5.
Sodium selenite (Na2SeO3, SSE) is an inorganic Se compound that is widely used in cancer chemoprevention studies. SSE has been shown to have anti-proliferative
effects on several types of human cancer cells, but its effect on osteosarcoma cells has thus far not been reported. In this
study, the cytotoxic effect of SSE on osteosarcoma cells U2OS was investigated in vitro and found to be higher than on comparable
non-cancer cell lines 293 and L6. Treatment with SSE decreased cell growth in a dose- and time-dependent manner and altered
cellular morphology. SSE also inhibited cell viability by inducing apoptosis, as evidenced by the formation of apoptotic bodies,
generation of reactive oxygen species (ROS), and accumulation of cells during the advanced phase of apoptosis. SSE-induced
apoptosis correlated with the activation of CASP 3, downregulation of BCL-2, and upregulation of P53 and PTEN in U2OS cells. These results indicated that SSE induces apoptosis in U2OS cells mainly through an ROS-mediated caspase pathway.
This is the first report to show a possible mechanism of the anti-proliferative effect of SSE for the prevention of osteosarcoma
in cell culture models. 相似文献
6.
Krumschnabel G Maehr T Nawaz M Schwarzbaum PJ Manzl C 《Apoptosis : an international journal on programmed cell death》2007,12(10):1755-1768
Apoptotic cell death in mammalian models is frequently associated with cell shrinkage. Inhibition of apoptotic volume decrease
(AVD) is cytoprotective, suggesting that cell shrinkage is an important early event in apoptosis. In salmonid hepatoma and
gill cells staurosporine induced apoptosis, as assessed by activation of effector caspases, nuclear condensation, and a decrease
of mitochondrial membrane potential (MMP), and these changes were accompanied by cell shrinkage. The Cl− transport inhibitor DIDS and the K+ channel inhibitor quinidine prevented AVD, but only DIDS inhibited apoptosis. Other Cl− flux inhibitors, as well as a pan-caspase inhibitor, did not prevent cell shrinkage, but still prevented caspase activation.
Furthermore, regulatory volume decrease (RVD) under hypotonic conditions was not facilitated, but diminished in apoptotic
cells. Since all transport inhibitors used blocked RVD, but only DIDS and quinidine inhibited AVD, the ion transporters involved
in both processes are apparently not identical. In addition, our data indicate that inhibition of Cl− fluxes rather than blocking cell shrinkage or K+ fluxes is important for preventing apoptosis. In line with this, inhibition of MAP kinases reduced RVD and not AVD, but still
diminished caspase activation. Finally, we observed that MAP kinases were activated upon staurosporine treatment and that
at least activation of ERK was prevented when AVD was inhibited. 相似文献
7.
Grzegorz Stasiłojć Sandra Pinto Roksana Wyszkowska Magda Wejda Ewa M. Słomińska Martyna Filipska Patrycja Koszałka Julian Świerczyński Jose Enrique O’Connor Jacek Jerzy Bigda 《Cellular & molecular biology letters》2013,18(2):249-262
The variant cell line U937V was originally identified by a higher sensitivity to the cytocidal action of tumor necrosis factor alpha (TNFα) than that of its reference cell line, U937. We noticed that a typical morphological feature of dying U937V cells was the lack of cellular disintegration, which contrasts to the formation of apoptotic bodies seen with dying U937 cells. We found that both TNFα, which induces the extrinsic apoptotic pathway, and etoposide (VP-16), which induces the intrinsic apoptotic pathway, stimulated U937V cell death without cell disintegration. In spite of the distinct morphological differences between the U937 and U937V cells, the basic molecular events of apoptosis, such as internucleosomal DNA degradation, phosphatidylserine exposure on the outer leaflet of the plasma membrane, caspase activation and cytochrome c release, were evident in both cell types when stimulated with both types of apoptosis inducer. In the U937V cells, we noted an accelerated release of cytochrome c, an accelerated decrease in mitochondrial membrane potential, and a more pronounced generation of reactive oxygen species compared to the reference cells. We propose that the U937 and U937V cell lines could serve as excellent comparison models for studies on the mechanisms regulating the processes of cellular disintegration during apoptosis, such as blebbing (zeiosis) and apoptotic body formation. 相似文献
8.
Gröbner S Autenrieth SE Soldanova I Gunst DS Schaller M Bohn E Müller S Leverkus M Wesselborg S Autenrieth IB Borgmann S 《Apoptosis : an international journal on programmed cell death》2006,11(11):1959-1968
Yersinia outer protein P (YopP) is a virulence factor of Yersinia enterocolitica that is injected into the cytosol of host cells where it targets MAP kinase kinases (MKKs) and inhibitor of κB kinase (IKK)-β
resulting in inhibition of cytokine production as well as induction of apoptosis in murine macrophages and dendritic cells
(DC). Here we show that DC death was only partially prevented by the broad spectrum caspase inhibitor zVAD-fmk, indicating
simultaneous caspase-dependent and caspase-independent mechanisms of cell death induction by YopP. Microscopic analyses and
measurement of cell size demonstrated necrosis-like morphology of caspase-independent cell death. Application of zVAD-fmk
prevented cleavage of procaspases and Bid, decrease of the inner transmembrane mitochondrial potential ΔΨm and mitochondrial release of cytochrome c. From these data we conclude that YopP-induced activation of the mitochondrial
death pathway is mediated upstream via caspases. In conclusion, our results suggest that YopP simultaneously induces caspase-dependent
apoptotic and caspase-independent necrosis-like death in DC. However, it has to be resolved if necrosis-like DC death occurs
independently from apoptotic events or as an apoptotic epiphenomenon. 相似文献
9.
《Bioscience, biotechnology, and biochemistry》2013,77(6):1163-1168
Fucoidan induces apoptosis by activating caspase-8 in human MCF-7 breast cancer cells, but the detailed mechanism for this is not understood. We demonstrate here that fucoidan interacted with the cell surface, and silencing the β1-integrin gene expression inhibited fucoidan-induced apoptosis accompanied by caspase-8 activation. Fucoidan induced formation of the β1-integrin-caspase-8 complex. These data indicate that β1-integrin is an important factor for the cell-surface binding of fucoidan and plays an important role in fucoidan-induced apoptosis. Fucoidan also induced recruitment of caspase-8 to the β1-integrin intracellular domain, cleaved it into the activated protein by direct combination with β1-integrin, and induced apoptosis via the caspase cascade in MCF-7 cells. 相似文献
10.
Methyl 3,5-dicaffeoyl quinate (MDQ) is a flavonoid glucoside found in several plants that scavenges 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals and peroxynitrite, and inhibits the formation of cholesteryl ester hydroperoxide during the copper ion-induced oxidation of blood plasma in rats. In this study, MDQ inhibited proliferation and induced apoptosis in HT-29 cells in a dose-dependent manner as detected by 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT), trypan blue exclusion, and flow cytometric assays. Western blot analysis showed that apoptosis was dependent on caspase-3 activity. PARP cleavage and the cytosolic release of cytochrome c from mitochondria increased significantly. In addition, these events were accompanied by a collapse in the mitochondrial membrane potential and a decreased Bcl-2/Bax ratio. Furthermore, the MDQ-induced G0/G1 arrest was correlated with an increase in p27 and a decrease in cyclin D1 and p53. MDQ also inhibited the phosphorylation of PI3K/Akt and ERK; significantly reduced NF-κB; and in general displayed a significant anti-proliferative effect via a cell cycle arrest and apoptotic induction in HT-29 cells. These results suggest that MDQ has therapeutic potential against human colon carcinoma. 相似文献
11.
Acrylamide (ACR), a potent neurotoxin, can be produced during food processing at high temperature. This study examined the redox-dependent apoptotic and inflammatory responses of ACR in an immortalized mouse microglia cell line BV2. The exposure of BV2 cells to ACR reduced cell viability and induced apoptosis in a concentration-dependent manner. ACR impaired cell energy metabolism by decreasing mitochondrial respiration, anaerobic glycolysis, and lowering expression of the complex I, III, and IV subunits. Mitochondrial dysfunction was associated with a decrease of the mitochondrial membrane potential and the Bcl-2/Bax ratio, thus resulting in activation of the mitochondrion-driven apoptotic signaling. This was accompanied by (a) the modulation of redox-sensitive signaling, suppressed Akt activation and increased JNK and p38 activation, and (b) increased expression of NFκB and downstream inducible nitric oxide synthase (iNOS) and nitric oxide generation, thus supporting indirectly a proinflammatory effect of ACR. Nrf2 expression was also increased but not its translocation to the nucleus. Expectedly, the electrophilic attack of ACR on GSH resulted in substantial loss of GSH with a minor GSSG formation. These changes in the cell׳s redox status elicited by ACR resulted in increased H2O2 formation. The changes in mitochondrial functionality and complex subunit expression caused by ACR were reversed by N-acetyl-L-cysteine (NAC). Likewise, NAC restored the cell׳s redox status by increasing GSH levels with concomitant attenuation of H2O2 generation; these effects resulted in decreased apoptotic cell death and inflammatory responses. ACR-mediated mitochondrial dysfunction along with a more oxidized redox status seems to be critical events leading to activation of the intrinsic apoptotic pathway and inflammatory responses. 相似文献
12.
Torres F Quintana J Díaz JG Carmona AJ Estévez F 《Apoptosis : an international journal on programmed cell death》2008,13(5):716-728
In the present study we demonstrated that the flavonoid derivative trifolin acetate (TA), obtained by acetylation of naturally
occurring trifolin, induces apoptosis. Associated downstream signaling events were also investigated. TA-induced cell death
was prevented by the non-specific caspase inhibitor z-VAD-fmk and reduced by the presence of the selective caspase inhibitors
z-LEHD-fmk (caspase-9), z-DEVD-fmk (caspase-3) and z-VEID-fmk (caspase-6). The apoptotic effect of TA was associated with
(i) the release of cytochrome c from mitochondria which was not accompanied by dissipation of the mitochondrial membrane potential (ΔΨm), (ii) the activation of the mitogen-activated protein kinases (MAPKs) pathway and (iii) abrogated by the over-expression
of Bcl-2 or Bcl-xL. TA-induced cell death was attenuated by inhibition of extracellular signal-regulated kinases (ERK) 1/2 with U0126 and inhibition
of p38MAPK with SB203580. In contrast, inhibition of c-Jun NH2-terminal kinase (JNK) by SP600125 significantly enhanced apoptosis. Although reactive oxygen species (ROS) increased in response
to TA, this did not seem to play a pivotal role in the apoptotic process since different anti-oxidants were unable to provide
cell protection. The present study demonstrates that TA-induced cell death is mediated by an intrinsic-dependent apoptotic
event involving mitochondria and MAPK, and through a mechanism independent of ROS generation. 相似文献
13.
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
14.
Ying S Häcker G 《Apoptosis : an international journal on programmed cell death》2007,12(11):2003-2011
Apoptotic cell death is characterized by the activation of the apoptotic signal transduction pathway on one hand and a number
of regularly found morphological and biochemical features, such as nuclear condensation and mitochondrial depolarisation.
Although much of our knowledge of apoptosis was obtained using noxious stimuli in cell culture, these apoptotic stimuli are
likely to have numerous off-target effects that may contribute to or obscure the immediate effects of the apoptotic pathway.
We have developed a cellular model where mitochondrial apoptosis is directly triggered by the tetracycline-regulated expression
of the pro-apoptotic BH3-only protein BimS. We report the comparison of BimS-induced apoptosis with the commonly used apoptotic stimuli staurosporine and UV-light. While the release of mitochondrial
cytochrome c and Smac/DIABLO, activation of caspases and nuclear morphological changes occurred with very similar kinetics, striking differences
were found in other apoptotic assays. In particular, drop in mitochondrial membrane potential, loss of plasma membrane integrity
and the appearance of sub-G1 nuclei were strongly reduced in cells dying upon BimS-induction, compared to staurosporine- or UV-induced apoptosis. The results thus indicate that the link between the apoptotic
pathway and commonly used indicators of apoptosis is less tight than it appears from experiments with cytotoxic stimuli. 相似文献
15.
Wang Z Liang R Huang GS Piao Y Zhang YQ Wang AQ Dong BX Feng JL Yang GR Guo Y 《Apoptosis : an international journal on programmed cell death》2006,11(10):1851-1860
Cathepsin D (cat D) reportedly plays an important role in certain apoptotic processes, the downstream pathways of which involve
release of cytochrome c (cyt c) from mitochondria and activation of the caspase cascade. Previous studies revealed that the B-cell lymphoma 2 (Bcl-2) family
members Bax or Bid play important roles in apoptotic signal transduction between cat D and mitochondria. Here, we show that
glucosamine sulfate (GS) inhibits the proliferation and induces apoptosis of human chronic myelogenous leukemia K562 cells
in vitro. GS interfered with the maturation of cat D. Activation of caspase-3, cleavage of poly-(ADP-ribose)-polymerase, release of
cyt c, and downregulation of Bcl-xL accompanied GS-induced apoptosis, and these processes were inhibited by the cat D inhibitor
pepstatin A. However, we did not detect any altered gene expression of Bcl-2, Bax, or Bid during apoptosis. Translocation
of cat D from the lysosome to the cytosol was observed in GS-treated K562 cells. These findings suggest that GS-induced K562
cell apoptosis involves the translocation of cat D from the lysosome to the cytosol. Furthermore, our findings suggest that
downregulation of Bcl-xL (but not Bcl-2, Bax, or Bid) connects cat D and the mitochondrial pathway, which causes the release
of cyt c and activation of the caspase cascade during GS-induced apoptosis of K562 cells. 相似文献
16.
Although resveratrol, an active ingredient derived from grapes and red wine, possesses chemopreventive properties against
several cancers, the molecular mechanisms by which it inhibits cell growth and induces apoptosis have not been clearly understood.
Here, we examined the molecular mechanisms of resveratrol and its interactive effects with TRAIL on apoptosis in prostate
cancer PC-3 and DU-145 cells. Resveratrol inhibited cell viability and colony formation, and induced apoptosis in prostate
cancer cells. Resveratrol downregulated the expression of Bcl-2, Bcl-XL and survivin and upregulated the expression of Bax, Bak, PUMA, Noxa, and Bim, and death receptors (TRAIL-R1/DR4 and TRAIL-R2/DR5).
Treatment of prostate cancer cells with resveratrol resulted in generation of reactive oxygen species (ROS), translocation
of Bax to mitochondria and subsequent drop in mitochondrial membrane potential, release of mitochondrial proteins (cytochrome
c, Smac/DIABLO, and AIF) to cytosol, activation of effector caspase-3 and caspase-9, and induction of apoptosis. Resveratrol-induced
ROS production, caspase-3 activity and apoptosis were inhibited by N-acetylcysteine. Bax was a major proapoptotic gene mediating the effects of resveratrol as Bax siRNA inhibited resveratrol-induced
apoptosis. Resveratrol enhanced the apoptosis-inducing potential of TRAIL, and these effects were inhibited by either dominant
negative FADD or caspase-8 siRNA. The combination of resveratrol and TRAIL enhanced the mitochondrial dysfunctions during
apoptosis. These properties of resveratrol strongly suggest that it could be used either alone or in combination with TRAIL
for the prevention and/or treatment of prostate cancer. 相似文献
17.
So-Jung Won Kyung-Sook Chung Yo Sook Ki Jung-Hye Choi Won-Jea Cho Kyung-Tae Lee 《Bioorganic & medicinal chemistry letters》2010,20(22):6447-6451
In the present study, we investigated the effect of a novel 3-arylisoquinoline derivative 3-(6-ethyl-benzo[1,3]dioxol-5-yl)-7,8-dimethoxy-2-methyl-2H-isoquinolin-1-one (CWJ-081) on the induction of apoptosis and the putative molecular mechanism of its action in human leukemia cells. Treatment with CWJ-081 exhibited a characteristic feature of apoptosis including externalization of phosphatidylserine and formation of DNA fragmentation in human leukemia cell lines (HL-60, U-937, K-562). In addition, stimulation of HL-60 cells with CWJ-081 induced a series of intracellular events: (1) the activations of caspase-8, -9, and -3; (2) the cleavage of poly (ADP-ribose) polymerase-1 (PARP-1); (3) the loss of mitochondrial membrane potential (ΔΨm); (4) the release of cytochrome c; and (5) the modulation of Bcl-2 family proteins. We further demonstrated that CWJ-081 induces reactive oxygen species (ROS) production and c-Jun NH2-terminal kinase (JNK) activation. Pretreatment with the antioxidant N-acetyl-l-cysteine (NAC) markedly inhibited the CWJ-081-induced JNK activation and apoptosis. Moreover, CWJ-081-induced apoptosis was suppressed in the presence of SP600125, a specific JNK inhibitor. Taken together, these data suggest that CWJ-081 induces apoptosis via the mitochondrial apoptotic pathway in HL-60 cells, and ROS-mediated JNK activation plays a key role in the CWJ-081-induced apoptosis. 相似文献
18.
Paloma Navarro Angela M. Valverde Ruben Conejo Manuel Benito Margarita Lorenzo 《Experimental cell research》1999,246(2):301
Serum deprivation of the immortalized brown adipocyte cell line resulted in growth arrest inG0/G1phases of the cell cycle and apoptosis, as detected by DNA laddering, nuclei condensation and fragmentation, and an increase in the percentage of hypodiploid cells. In addition, apoptosis in these cells is accompanied by an induction of the expression of the apoptotic form of the Bcl-x gene, the isoform Bcl-xS, and by a decrease of Bcl-2 expression, Bcl-xL remaining almost undetectable. The loss of mitochondrial membrane potential was associated with apoptosis. Z-VAD, a cell-permeable inhibitor of caspases, but not cycloheximide, precludes DNA laddering under serum deprivation. Moreover, Z-VAD rescues serum-deprived brown adipocytes from apoptosis, decreasing the percentage of hypodiploid cells, the percentage of apoptotic cells under Tunnel assay, and the external display of phosphatidylserine. More importantly, Z-VAD survival effects on immortalized brown adipocytes concur with a downregulation of Bcl-xS mRNA/protein and an upregulation of Bcl-2 protein content. Ultimately, Z-VAD prevents the loss of mitochondrial membrane potential. 相似文献
19.
Sophie Camilleri-Broët Holly Vanderwerff Elizabeth Caldwell David Hockenbery 《Experimental cell research》1998,239(2):277
Recent studies have shown that reduction in mitochondrial membrane potential (ΔΨm) and generation of reactive oxygen species are early events in apoptosis. In this study, we present two different models of apoptotic cell death, Chinese hamster ovary (CHO) cells treated with aphidicolin and dexamethasone-treated 2B4 T-cell hybridoma cells, which display opposing mitochondrial changes. CHO cells arrested at G1/S with aphidicolin have a progressive increase in mitochondria mass and number, assessed by flow cytometry and fluorescent microscopy with mitochondria-specific probes. The increase in mitochondrial mass was not accompanied by a gain in net cellular mitochondrial membrane potential, consistent with an accumulation of relatively depolarized mitochondria. Fluorescent microscopy demonstrated an increased content of low ΔΨmmitochondria in aphidicolin-treated CHO cells, but high ΔΨmmitochondria were also present and remained stable in number. Mitochondrial mass correlated with decreased clonogenicity of aphidicolin-treated CHO cells. Cycloheximide prevented both the proliferation of mitochondria and subsequent cell death. In contrast, dexamethasone treatment of 2B4 T-cell hybridoma cells caused a decrease in ΔΨmwithout mitochondrial proliferation. Cycloheximide and Bcl-2 overexpression inhibited the loss of ΔΨm, as well as apoptosis. In both models, cell death was associated with a decrease in mitochondrial potential relative to mitochondrial mass, suggesting that an accumulation of damaged or dysfunctional mitochondria had occurred. 相似文献
20.
N‐(3‐Oxo‐acyl)‐homoserine lactone induces apoptosis primarily through a mitochondrial pathway in fibroblasts
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Guoping Zhao Christian Schwarzer Nicole S. Stivers Aaron G. Whitt Shuhan Meng Joseph A. Burlison Terry E. Machen Chi Li 《Cellular microbiology》2018,20(1)
N‐(3‐Oxododecanoyl)‐l ‐homoserine lactone (C12) is produced by Pseudomonas aeruginosa to function as a quorum‐sensing molecule for bacteria–bacteria communication. C12 is also known to influence many aspects of human host cell physiology, including induction of cell death. However, the signalling pathway(s) leading to C12‐triggered cell death is (are) still not completely known. To clarify cell death signalling induced by C12, we examined mouse embryonic fibroblasts deficient in “initiator” caspases or “effector” caspases. Our data indicate that C12 selectively induces the mitochondria‐dependent intrinsic apoptotic pathway by quickly triggering mitochondrial outer membrane permeabilisation. Importantly, the activities of C12 to permeabilise mitochondria are independent of activation of both “initiator” and “effector” caspases. Furthermore, C12 directly induces mitochondrial outer membrane permeabilisation in vitro. Overall, our study suggests a mitochondrial apoptotic signalling pathway triggered by C12, in which C12 or its metabolite(s) acts on mitochondria to permeabilise mitochondria, leading to activation of apoptosis. 相似文献