共查询到20条相似文献,搜索用时 15 毫秒
1.
The inflammatory mediator nitric oxide (NO*) promotes apoptotic cell death based on morphological evidence, accumulation of the tumor suppressor p53, caspase-3 activation, and DNA fragmentation in RAW 264.7 macrophages. Since nitrosothiols may actually be the predominant form of biologically active NO* in vivo, we used S-nitrosoglutathione (GSNO) to study activation of extracellular signal-regulated protein kinases1/2 (ERK1/2), c-Jun N-terminal kinases/stress-activated protein kinases (JNK1/2), and p38 kinases. Moreover, we determined the role of mitogen-activated protein kinase signaling in the apoptotic transducing ability of GSNO. ERK1/2 became activated in response to GSNO after 4 h and remained active for the next 20 h. Blocking the ERK1/2 pathway by the mitogen-activated protein kinase kinase inhibitor PD 98059 enhanced GSNO-elicited apoptosis. p38 was activated as well, but inhibition of p38 with SB 203580 left apoptosis unaltered. Activation of JNK1/2 by GSNO showed maximal kinase activities between 2 and 8 h. Attenuating JNK1/2 by antisense-depletion eliminated the pro-apoptotic action of low GSNO concentrations (250 microM), whereas apoptosis proceeded independently of JNK1/2 at higher doses of the NO donor (500 microM). Decreased apoptosis by JNK1/2 depletion prevented p53 accumulation after the addition of GSNO, which positions JNK1/2 upstream of the p53 response at low agonist concentrations. In line, JNK1/2 activation proceeded unaltered in p53-antisense transfected macrophages. However, with higher GSNO concentrations apoptotic transducing pathways, including p53 accumulation, were JNK1/2 unrelated. The regulation of mitogen-activated protein kinases by GSNO may help to define cell protective and destructive actions of reactive nitrogen species. 相似文献
2.
Axin negatively regulates the Wnt pathway during axis formation and plays a central role in cell growth control and tumorigenesis. We found that Axin also serves as a scaffold protein for mitogen-activated protein kinase activation and further determined the structural requirement for this activation. Overexpression of Axin in 293T cells leads to differential activation of mitogen-activated protein kinases, with robust induction for c-Jun NH(2)-terminal kinase (JNK)/stress-activated protein kinase, moderate induction for p38, and negligible induction for extracellular signal-regulated kinase. Axin forms a complex with MEKK1 through a novel domain that we term MEKK1-interacting domain. MKK4 and MKK7, which act downstream of MEKK1, are also involved in Axin-mediated JNK activation. Domains essential in Wnt signaling, i. e. binding sites for adenomatous polyposis coli, glycogen synthase kinase-3beta, and beta-catenin, are not required for JNK activation, suggesting distinct domain utilization between the Wnt pathway and JNK signal transduction. Dimerization/oligomerization of Axin through its C terminus is required for JNK activation, although MEKK1 is capable of binding C terminus-deleted monomeric Axin. Furthermore, Axin without the MEKK1-interacting domain has a dominant-negative effect on JNK activation by wild-type Axin. Our results suggest that Axin, in addition to its function in the Wnt pathway, may play a dual role in cells through its activation of JNK/stress-activated protein kinase signaling cascade. 相似文献
3.
Serine/threonine protein phosphatases are important mediators of general cellular function as well as neurodegenerative processes. We have previously shown inhibition of protein phosphatases to be as neurotoxic as glutamate-induced neuronal death but resistant to neuroprotection by estrogens. In this study, the mechanism by which phosphatase inhibition via okadaic acid (OA) induced neurotoxicity is explored. Neurons were exposed to OA or glutamate in the presence or absence of various protein kinases inhibitors, and/or one of four estrogens. Both OA and glutamate induced cell death via increased reactive oxygen species, protein carbonylation, lipid peroxidation, caspase-3 activity, and mitochondrial dysfunction. All estrogens attenuated glutamate-mediated responses, but not OA-induced responses. In addition, inhibition of protein kinase C and mitogen-activated protein kinase pathway was neuroprotective against glutamate but not OA toxicity. Interestingly, inhibition of mitogen-activated protein kinase pathway with PD98096 or U0126 caused a decrease in reactive oxygen species production suggesting that activation of ERK1/2 could further exacerbate the oxidative stress caused by glutamate-induced toxicity; however, these inhibitors had no effect on OA-induced toxicity. Collectively, these results indicate that both glutamate and OA neurotoxicities are mediated by persistent activation of ERK1/2 and/or protein kinase C and a resulting oxidative stress, and that protein phosphatase activity is an important and necessary aspect of estrogen-mediated neuroprotection. 相似文献
4.
Iria Carballo-Carbajal Susanne Weber-Endress Giorgio Rovelli Diane Chan Benjamin Wolozin Christian L. Klein Nadja Patenge Thomas Gasser Philipp J. Kahle 《Cellular signalling》2010,22(5):821-827
Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most frequent cause of autosomal-dominant Parkinson's disease (PD). The second known autosomal-dominant PD gene (SNCA) encodes α-synuclein, which is deposited in Lewy bodies, the neuropathological hallmark of PD. LRRK2 contains a kinase domain with homology to mitogen-activated protein kinase kinase kinases (MAPKKKs) and its activity has been suggested to be a key factor in LRRK2-associated PD. Here we investigated the role of LRRK2 in signal transduction pathways to identify putative PD-relevant downstream targets. Over-expression of wild-type [wt]LRRK2 in human embryonic kidney HEK293 cells selectively activated the extracellular signal-regulated kinase (ERK) module. PD-associated mutants G2019S and R1441C, but not kinase-dead LRRK2, induced ERK phosphorylation to the same extent as [wt]LRRK2, indicating that this effect is kinase-dependent. However, ERK activation by mutant R1441C and G2019S was significantly slower than that for [wt]LRRK2, despite similar levels of expression. Furthermore, induction of the ERK module by LRRK2 was associated to a small but significant induction of SNCA, which was suppressed by treatment with the selective MAPK/ERK kinase inhibitor U0126. This pathway linking the two dominant PD genes LRRK2 and SNCA may offer an interesting target for drug therapy in both familial and sporadic disease. 相似文献
5.
Christian Johannes Gloeckner Annette Schumacher Karsten Boldt† Marius Ueffing† 《Journal of neurochemistry》2009,109(4):959-968
Autosomal dominant mutations in the human Leucine-Rich Repeat Kinase 2 ( LRRK2 ) gene represent the most common monogenetic cause of Parkinson disease (PD) and increased kinase activity observed in pathogenic mutants of LRRK2 is most likely causative for PD-associated neurotoxicity. The sequence of the LRRK2 kinase domain shows similarity to MAP kinase kinase kinases. Furthermore, LRRK2 shares highest sequence homology with mixed linage kinases which act upstream of canonical MAPKK and are involved in cellular stress responses. Therefore, we addressed the question if LRRK2 exhibits MAPKKK activity by systematically testing MAPKKs as candidate substrates, in vitro . We demonstrate that LRRK2 variants phosphorylate mitogen-activated protein kinase kinases (MAPKK), including MKK3 -4, -6 and -7. MKKs act upstream of the MAPK p38 and JNK mediating oxidative cell stress, neurotoxicity and apoptosis. The disease-associated LRRK2 G2019S and I2020T mutations show an increased phosphotransferase activity towards MKKs correlating with the activity shown for its autophosphorylation. Our findings present evidence of a new class of molecular targets for mutant LRRK2 that link to neurotoxicity, cellular stress, cytoskeletal dynamics and vesicular transport. 相似文献
6.
Licorice (Glycyrrhiza uralensis) is a medicinal herb containing various bioactive components implicated in antioxidative, anti-inflammatory, antiviral, and neuroprotective effects, but the effects of licorice against Parkinson's disease (PD)-related dopaminergic cell death have not been studied. In this study, we investigated the protective effects of isoliquiritigenin (ISL) isolated from Glycyrrhiza uralensis on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in a dopaminergic cell line, SN4741. ISL (1 μM) significantly attenuated 6-OHDA (50 μM)-induced reactive oxygen species (ROS) and nitric oxide (NO) generation and apoptotic cell death. ISL pretreatment effectively suppressed 6-OHDA-mediated upregulation of Bax, p-c-Jun N-terminal kinase (JNK), p-p38 mitogen-activated protein (MAP) kinase, cytochrome c release, and caspase 3 activation. In addition, ISL significantly attenuated 6-OHDA-induced Bcl-2, brain-derived neurotrophic factor (BDNF), and mitochondrial membrane potential (MMP) reduction. Pharmacological inhibitors of the phosphatidylinositol 3-kinase (PI3K)-Akt/protein kinase B (PKB) pathway reversed ISL-mediated neuroprotection against 6-OHDA toxicity in SN4741 cells. These results provide the first evidence that ISL can protect dopaminergic cells under oxidative stress conditions by regulating the apoptotic process. 相似文献
7.
Offen D Gilgun-Sherki Y Barhum Y Benhar M Grinberg L Reich R Melamed E Atlas D 《Journal of neurochemistry》2004,89(5):1241-1251
Increasing evidence suggests that enhanced production of reactive oxygen species (ROS) activates the MAP kinases, c-Jun N-terminal protein kinase (JNK) and mitogen-activated protein kinase MAPK (p38). These phosphorylated intermediates at the stress-activated pathway induce expression of matrix metalloproteinases (MMPs), leading to inflammatory responses and pathological damages involved in the etiology of multiple sclerosis (MS). Here we report that N-acetylcysteine amide (AD4) crosses the blood-brain barrier (BBB), chelates Cu(2+), which catalyzes free radical formation, and prevents ROS-induced activation of JNK, p38 and MMP-9. In the myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, oral administration of AD4 drastically reduced the clinical signs, inflammation, MMP-9 activity, and protected axons from demylination damages. In agreement with the in vitro studies, we propose that ROS scavenging by AD4 in MOG-treated animals prevented MMP's induction and subsequent damages through inhibition of MAPK pathway. The low toxicity of AD4 coupled with BBB penetration makes this compound an excellent potential candidate for the therapy of MS and other neurodegenerative disorders. 相似文献
8.
Yong Ren Houbo Jiang Fang Yang Kazuhiro Nakaso Jian Feng 《The Journal of biological chemistry》2009,284(6):4009-4017
Mitogen-activated protein kinases, originally known as
microtubule-associated protein (MAP) kinases, are activated in response to a
variety of stimuli. Here we report that microtubule-depolymerizing agents such
as colchicine or nocodazole induced strong activation of MAP kinases including
JNK, ERK, and p38. This effect was markedly attenuated by parkin, whose
mutations are linked to Parkinson disease (PD). Our previous study has shown
that parkin stabilizes microtubules through strong interactions mediated by
three independent domains. We found that each of the three microtubule-binding
domains of parkin was sufficient to reduce MAP kinase activation induced by
microtubule depolymerization. The ability to attenuate microtubule
depolymerization and the ensuing MAP kinase activation was abrogated in
B-lymphocytes and fibroblasts derived from PD patients with parkin mutations
such as exon 4 deletion. Such mutations produced truncated parkin proteins
lacking any microtubule binding domain and prevented parkin from protecting
midbrain dopaminergic neurons against microtubule-depolymerizing toxins such
as rotenone or colchicine. Consistent with these, blocking MAP kinase
activation in midbrain dopaminergic neurons by knocking down MAP kinase
kinases (MKK) significantly reduced the selective toxicity of rotenone or
colchicine. Conversely, overexpression of MAP kinases caused marked toxicities
that were significantly attenuated by parkin. Thus, the results suggest that
parkin protects midbrain dopaminergic neurons against
microtubule-depolymerizing PD toxins such as rotenone by stabilizing
microtubules to attenuate MAP kinase activation.Mitogen-activated protein kinases are a superfamily of kinases that include
the extracellular signal-related kinases
(ERK1/2),2 Jun
N-terminal kinases (JNK1/2/3), and p38 proteins
(p38α/β/γ/δ) in mammalian species
(1). Initially, MAP kinase
stood for microtubule-associated protein kinase because microtubule-associated
proteins such as MAP2 are excellent substrates of MAP kinases
(2,
3). Previous studies have shown
that a significant portion of ERK is associated with microtubules
(4). It has also been shown
that JNK1 is required for the maintenance of microtubule integrity in neurons
through controlling the phosphorylation states of MAP2 and MAP1B
(5). Phosphorylation of tau, an
axon-enriched MAP, by p38δ promotes microtubule assembly
(6). All MAP kinases are
proline-directed kinases, preferring serine or threonine residues followed by
proline. The abundance of such sites on many microtubule-associated proteins
suggests that MAP kinases play critical roles in regulating the
phosphorylation states of MAPs; hence, the dynamic properties of
microtubules.The selective loss of dopaminergic (DA) neurons in substantia nigra is the
pathological hallmark of Parkinson disease and directly contributes to its
locomotor symptoms. Nigral DA neurons project to striatal target areas with
very long axons, which rely on microtubules to transport dopamine vesicles
over long distances. Our previous studies have shown that these dopaminergic
neurons are particularly vulnerable to microtubule-depolymerizing agents
including rotenone (7), an
environmental toxin that causes PD-like symptoms and pathologies in animal
models (8). Microtubule
depolymerization disrupts vesicular transport, which significantly elevates
oxidative stress due to increased oxidation of cytosolic dopamine leaked from
vesicles (7). On the other hand
our previous studies have shown that parkin, a protein-ubiquitin E3 ligase
linked to Parkinson disease, strongly binds to microtubules
(9) through redundant, high
affinity interactions mediated by three independent domains
(10). In addition, parkin
increases the ubiquitination and degradation of both α- and
β-tubulin (9), whose
complex folding reactions are prone to produce misfolded intermediates
(11). These results suggest
that parkin plays an important role in maintaining the stability and normal
functions of microtubules, which are critically involved in the survival of
nigral DA neurons (12).In the present study we examined the impact of parkin on MAP kinase
activation induced by microtubule depolymerization. Our results showed that
MAP kinases, including JNK, ERK, and p38, were activated by
microtubule-depolymerizing agents such as colchicine and nocodazole. This
effect was greatly attenuated by overexpression of wild-type parkin or any one
of its three microtubule binding domains. The ability of parkin to suppress
microtubule depolymerization and the ensuing MAP kinase activation was
abrogated in PD patients with parkin mutations such as exon 4 deletion, which
produced a truncated protein lacking any microtubule-binding domain. This
mutation also prevented parkin from protecting dopaminergic neurons against
the selective toxicity of microtubule-depolymerizing toxins such as rotenone
or colchicine. Blocking MAP kinase activation by small interfering RNA (siRNA)
of MAP kinase kinases significantly reduced the selective toxicity of rotenone
or colchicine, whereas overexpression of MAP kinases produced toxicities that
were significantly reduced by parkin. Together, the results suggest that
parkin protects midbrain dopaminergic neurons against
microtubule-depolymerizing PD toxins by stabilizing microtubules to rein in
MAP kinase activation. 相似文献
9.
The mast cell product tryptase, via protease-activated receptor 2 (PAR2), induces cyclooxygenase-2 (COX2) and 15-deoxy-prostaglandin J2 (15d-PGJ2) synthesis. 15d-PGJ2, through the nuclear peroxisome proliferator activated receptor gamma (PPARgamma), subsequently causes fibroblast proliferation. In this study we attempted to determine initial events of the tryptase/PAR2 signaling pathway leading to COX2 induction and fibroblast proliferation. In human fibroblasts (HFFF2), cDNA array, RT-PCR and Western blotting studies demonstrated that tryptase, but not 15d-PGJ2, up-regulates c-jun, c-fos and COX2 expression, and phosphorylates the extracellular signal-regulated kinase isoforms 1 and 2 (erk1/2). Furthermore, tryptase effects on erk1/2, c-jun, c-fos, COX2 and cell proliferation were prevented by PD98059, an inhibitor of the mitogen-activated protein kinase kinase (MEK). Other kinases [P38, stress-activated protein kinase/c-jun N-terminal kinase (SAPK/JUNK), erk5], intracellular Ca(2+) or cAMP were not affected by tryptase/PAR2. Our study identifies crucial intracellular events leading to induction of COX2 and fibroblast proliferation, i.e. a cornerstone of fibrosis. 相似文献
10.
Nicke B Bastien J Khanna SJ Warne PH Cowling V Cook SJ Peters G Delpuech O Schulze A Berns K Mullenders J Beijersbergen RL Bernards R Ganesan TS Downward J Hancock DC 《Molecular cell》2005,20(5):673-685
The ability of activated Ras to induce growth arrest of human ovarian surface epithelial (HOSE) cells via induction of the cyclin-dependent kinase inhibitor p21(WAF1/CIP1) has been used to screen for Ras pathway signaling components using a library of RNA interference (RNAi) vectors targeting the kinome. Two known Ras-regulated kinases were identified, phosphoinositide 3-kinase p110alpha and ribosomal protein S6 kinase p70(S6K1), plus the MAP kinase kinase kinase kinase MINK, which had not previously been implicated in Ras signaling. MINK is activated after Ras induction via a mechanism involving reactive oxygen species and mediates stimulation of the stress-activated protein kinase p38 MAPK downstream of the Raf/ERK pathway. p38 MAPK activation is essential for Ras-induced p21(WAF1/CIP1) upregulation and cell cycle arrest. MINK is thus a distal target of Ras signaling in the induction of a growth-arrested, senescent-like phenotype that may act to oppose oncogenic transformation in HOSE cells. 相似文献
11.
12.
Usuki F Takahashi N Sasagawa N Ishiura S 《Biochemical and biophysical research communications》2000,267(3):739-743
We investigated the response to oxidative stress in a model system established in C2C12 cells stably transfected with myotonin protein kinase (MtPK) cDNAs having 5, 46, 60, or 160 CTG repeats. The transformants showed CTG repeat number-dependent susceptibility to oxidative stress. Mutant MtPK cDNA transformants containing 160 CTG repeats showed apoptotic cell death by the exposure to an oxidant, a very low level of methylmercury. The addition of the antioxidant Trolox protected transformants against apoptosis. Oxidative stress activated the extracellular signal-regulated kinases (ERKs) pathway leading to cell survival in wild-type MtPK cDNA transformants, whereas mutant MtPK cDNA transformants having 160 CTG repeats were defective in the induction of the ERK pathway, although the activation of stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK) was strong and sustained. These results suggest that the susceptibility to oxidative stress in mutant MtPK cDNA transformants involves differential signaling pathways evoked following oxidative stress. 相似文献
13.
Activation of mitogen-activated protein (MAP) kinases has been reported to occur after a hypo-osmotic cell swelling in various types of cells. In renal epithelial A6 cells, the hypo-osmotic shock induced a rapid increase in the phosphorylation of an extracellular signal-regulated kinase (ERK)-like protein that was maximal 10 min after osmotic stress. Activation of ERK was significantly increased when hypo-osmotic stress was performed in the absence of extracellular Ca2+, a condition that inhibits regulatory volume decrease (RVD). Exposure of cells to PD98059, an inhibitor of the MAP kinase kinase MEK, at a concentration that fully cancelled ERK activation, did not inhibit RVD. On the contrary, RVD was abolished when osmotic shock was induced in the presence of SB203580, an inhibitor of stress-activated protein kinases (SAPKs). These results suggest that different MAP kinases are activated after hypo-osmotic stress in A6 cells. SAPKs would be involved in the control of RVD, while ERK would lead to later events, such as gene expression or energy metabolism. 相似文献
14.
15.
Mouse embryonic stem cells remain pluripotent when maintained in the presence of leukemia inhibitory factor (LIF). Upon LIF withdrawal, most cells differentiate into various lineages, while some die by apoptosis within 3 days. We have analyzed the activation pattern of the mitogen-activated protein kinase (MAPK) families and characterized the expression profile of selected genes modulated during differentiation or apoptosis. We show that p38 MAPKs are activated first, during the apoptotic crisis, while extracellular-regulated kinases and c-Jun N-terminal kinases are induced after the apoptotic crisis in differentiated cells. However, by using both p38 kinase inhibitors (PD169316 and SB203580) and a p38alpha(-/-) cell line, we demonstrate that p38alpha activation is rather a consequence than a cause of apoptosis. We thus reveal novel properties of PD169316, which induces cell survival without impairing cell differentiation, and identify PD169316-sensitive targets like the fibroblast growth factor-5, Brachyury and bcl-2 genes. Finally, we demonstrate that overexpression of the PD169316 - regulated bcl-2 gene prevents LIF withdrawal - induced cell death. 相似文献
16.
Gu-Choul Shin Changyoun Kim Jong-Min Lee Wang-Sik Cho Sang-Gyu Lee Mini Jeong Jaewook Cho Kyungho Lee 《Chemico-biological interactions》2009,182(1):29-36
Fibroblast-like synovial cells play a crucial role in the pathophysiology of rheumatoid arthritis (RA), as these cells are involved in inflammation and joint destruction. Apigenin, a dietary plant-flavonoid, is known to have many functions in animal cells including anti-proliferative and anticancer activities, but its role in human rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) has not been reported. In this study, we investigated the roles of apigenin in RA-FLSs. The survival rate decreased, and apoptotic cell death was induced by apigenin treatment in RA-FLSs. Apigenin treatment resulted in activation of the mitogen-activated protein kinase (MAPK) ERK1/2, and pretreatment with an ERK inhibitor PD98059 dramatically reduced apigenin-induced apoptosis. We found that apigenin-mediated production of a large amount of intracellular reactive oxygen species (ROS) caused activation of ERK1/2 and apoptosis; treatment with the antioxidant Tiron strongly inhibited the apigenin-induced generation of ROS, phosphorylation of ERK1/2, and apoptotic cell death. Apigenin-induced apoptotic cell death was mediated through activation of the effectors caspase-3 and caspase-7, and was blocked by pretreatment with Z-VAD-FMK (a pan-caspase inhibitor). These results showed that apigenin-induced ROS and oxidative stress-activated ERK1/2 caused apoptotic cell death in apigenin-treated RA-FLSs. 相似文献
17.
《Bioscience, biotechnology, and biochemistry》2013,77(3):536-543
Licorice (Glycyrrhiza uralensis) is a medicinal herb containing various bioactive components implicated in antioxidative, anti-inflammatory, antiviral, and neuroprotective effects, but the effects of licorice against Parkinson’s disease (PD)-related dopaminergic cell death have not been studied. In this study, we investigated the protective effects of isoliquiritigenin (ISL) isolated from Glycyrrhiza uralensis on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in a dopaminergic cell line, SN4741. ISL (1 μM) significantly attenuated 6-OHDA (50 μM)-induced reactive oxygen species (ROS) and nitric oxide (NO) generation and apoptotic cell death. ISL pretreatment effectively suppressed 6-OHDA-mediated upregulation of Bax, p-c-Jun N-terminal kinase (JNK), p-p38 mitogen-activated protein (MAP) kinase, cytochrome c release, and caspase 3 activation. In addition, ISL significantly attenuated 6-OHDA-induced Bcl-2, brain-derived neurotrophic factor (BDNF), and mitochondrial membrane potential (MMP) reduction. Pharmacological inhibitors of the phosphatidylinositol 3-kinase (PI3K)-Akt/protein kinase B (PKB) pathway reversed ISL-mediated neuroprotection against 6-OHDA toxicity in SN4741 cells. These results provide the first evidence that ISL can protect dopaminergic cells under oxidative stress conditions by regulating the apoptotic process. 相似文献
18.
Kim SY Ryu SJ Kang HT Choi HR Park SC 《Apoptosis : an international journal on programmed cell death》2011,16(8):795-807
In order to study the nature of aging-dependent apoptosis resistance, we compared the activation pattern of mitogen-activated
protein kinases (MAPK) in response to three different stress modalities: hydrogen peroxide (H2O2), staurosporine, and thapsigargin. We observed the agonist-specific activation pattern of MAP kinases in human diploid fibroblasts
(HDFs). When young HDFs were treated with PD98059, a specific inhibitor of extracellular signal-regulated kinase (ERK), H2O2-induced apoptosis was blocked, whereas staurosporine-induced apoptosis was inhibited by treatment with SB203580, a specific
inhibitor of p38. In addition, the levels of anti-apoptotic protein Bcl-2 (B-cell lymphoma protein-2) were restored by PD98059
or SB239063 in cells treated with H2O2 or staurosporine, respectively. We also found that inhibition of the nuclear import of p-Erk and p-p38 using wheat germ agglutinin
induced apoptosis resistance in young HDF cells in response to H2O2 or staurosporine. These data indicate a potential role of the nuclear translocation of apoptotic signals in the induction
of apoptosis. Moreover, the nuclear translocation of activated ERK1/2 and p38 in response to H2O2 or staurosporine was significantly compromised in senescent HDFs, compared with young cells. Taken together, we propose that
the apoptosis resistance of senescent HDFs might be related to the defective nuclear translocation of stress-activated signals
in an agonist-specific manner, which would imply the operation of an aging-dependent functional nucleo-cytoplasmic trafficking
barrier. 相似文献
19.
20.
Regulation of TNF expression by multiple mitogen-activated protein kinase pathways 总被引:16,自引:0,他引:16
Zhu W Downey JS Gu J Di Padova F Gram H Han J 《Journal of immunology (Baltimore, Md. : 1950)》2000,164(12):6349-6358