Apoptosis Signaling Pathway in T Cells Is Composed of ICE/Ced-3 Family Proteases and MAP Kinase Kinase 6b

Huang, Shuang; Jiang, Yong; Li, Zhuangjie; Nishida, Eisuke; Mathias, Patricia; Lin, Sheng-Cai; Ulevitch, Richard J.; Nemerow, Glen R.; Han, Jiahuai

doi:10.1016/s1074-7613(00)80449-5

Cited by 221 publications

(216 citation statements)

References 65 publications

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“…5G). As p38 À/À ES cells were not available to us, we created ES cell clones expressing a dominant negative form of the p38-upstream activating kinase MKK6 (MKK6b) [42]. As expected, two independent cell lines (DN-C1 and DN-C3), but not control (empty vector) cells, failed to upregulate phosphorylated p38 in serum (Fig.…”

Section: Resultsmentioning

confidence: 65%

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Mitochondrial Reactive Oxygen Species Mediate Cardiomyocyte Formation from Embryonic Stem Cells in High Glucose

et al. 2010

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Accumulating evidence points to reactive oxygen species (ROS) as important signaling molecules for cardiomyocyte differentiation in embryonic stem (ES) cells. Given that ES cells are normally maintained and differentiated in medium containing supraphysiological levels of glucose (25 mM), a condition which is known to result in enhanced cellular ROS formation, we questioned whether this high glucose concentration was necessary for cardiomyocyte lineage potential. We show here that ES cells cultured in physiological glucose (5 mM), maintained their general stemness qualities but displayed an altered mitochondrial metabolism, which resulted in decreased ROS production. Furthermore, ES and induced pluripotent stem (iPS) cells differentiated in lower glucose concentrations failed to generate cardiomyocyte structures; an effect mimicked with antioxidant treatments using catalase, N-acetyl cysteine and mitoubiquinone, under high glucose conditions in ES cells. Molecular analysis revealed that ES cells differentiated in 5 mM glucose had reduced expression of the pro-cardiac NOX4 gene and diminished phosphorylation of p38 mitogen-activated protein kinase (MAPK), together with specific changes in the cardiac transcriptional network. These outcomes could be reversed by supplementation of low glucose cultures with ascorbic acid, paradoxically acting as a pro-oxidant. Furthermore, forced expression of an upstream p38 MAPK kinase (MKK6) could bypass the requirement for ROS during differentiation to cardiomyocytes under low glucose conditions, illustrating a key role for p38 in the cardiac differentiation program. Together these data demonstrate that endogenous ROS control is important for cardiomyocyte formation from ES cells, and furthermore that supraphysiological glucose, by supplying ROS, is absolutely required.

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Section: Resultsmentioning

confidence: 65%

“…5H). To directly activate the p38 MAPK pathway, we next overexpressed a constitutively active form of the upstream activator of p38, MKK6b(E) [42]. Analysis of an overexpressing clone showed that p38 phosphorylation was enhanced under conditions of serum starvation (Fig.…”

Section: Resultsmentioning

confidence: 99%

Mitochondrial Reactive Oxygen Species Mediate Cardiomyocyte Formation from Embryonic Stem Cells in High Glucose

et al. 2010

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“…Ohtsuka 27 et al have shown that chemotherapy agents such as adriamycin and cisplatin enhanced TRAIL receptor agonistic antibody-mediated apoptosis by activation of P38 MAP kinase and JNK because inhibition of p38 MAP kinase and JNK activation suppressed the enhanced apoptotic effect by adriamycin or cisplatin.On the other hand, it is reported that p38 MAP kinases were activated in Jurkat T cells treated with FasL, however, this activation is not required for apoptosis induced by Fas L. 34,35 Because MAP kinases were involved in secretion of cytokines, such as TNF-α, IL-1β and IL-6, 20 it is possible that activation of MAP kinase in different cell environments may lead to secretion of different cytokines, which may coordinate the balance between cell survival and or cell death.…”

Section: Discussionmentioning

confidence: 99%

Lack of p38 MAP Kinase Activation in TRAIL-Resistant Cells is Not Related to the Resistance to TRAIL-Mediated Cell Death

Zhang

Zhu

Davis

et al. 2004

Cancer Biology & Therapy

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Activation of MAP kinases is involved in various cellular processes, including immunoregulation, inflammation, cell growth, cell differentiation, and cell death. To investigate the role of p38 MAP kinase activation in the signaling pathway of TRAIL-mediated apoptosis, we compared TRAIL-mediated MAP kinase activation in TRAIL-susceptible human colon cancer cell line DLD1 and TRAIL-resistant DLD1/TRAIL-R cells. TRAIL-mediated activation of ERK occurred in both cell lines. In contrast, both DLD1 and DLD1/TRAIL-R cells showed no obvious JNK activation after treatment with TRAIL. Interestingly, TRAIL-mediated activation of p38 MAP kinases was observed in DLD1 cells but not in DLD1/TRAIL-R cells. However, activation of p38 MAP kinases was observed in both DLD1 and DLD1/TRAIL-R cells after treatment with anisomycin. Furthermore, inhibiting activated p38 MAP kinases with known inhibitors or with an adenovector expressing dominant negative p38α did not block TRAIL-mediated cell death in DLD1 cells. Moreover, activation of p38 MAP kinases by adenovectors expressing constitutive MKK3 or MKK6 (Ad/MKK3bE or Ad/MKK6bE) did not induce cell death in either DLD1 or DLD1/TRAIL-R cell lines. Our results suggest that activation of p38 MAP kinases does not play a major role in TRAIL-mediated apoptosis in DLD1 cells and that lack of TRAIL-mediated p38 MAP kinase activation may not be the mechanism of TRAIL-resistance in DLD1/TRAIL-R cells. INTRODUCTIONThe tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor (TNF) superfamily. Like the other two members of this superfamily TNF-α and Fas ligand, TRAIL has strong antitumor activity both in vitro and in vivo in a wide range of cancer cell types. 1 Unlike TNF-α and Fas ligand, however, TRAIL exhibits minimal cytotoxity to most of normal cells and tissues and, therefore, shows potential of its becoming a new therapeutic agent for cancer treatment. [2][3][4] For most cell types, TRAIL induces cell death through apoptosis. Although the detailed mechanisms of the signaling pathway of TRAIL-induced apoptosis are still unclear, some important components and steps in the signaling pathway have already been elucidated. The interaction of TRAIL and its two death receptors, DR4 (TRAIL-R1) and/or DR5 (TRAIL-R2), is the initial step of TRAIL-induced apoptosis. 5,6 The binding of TRAIL to its receptors leads to trimerization and activation of the death receptors. The activated death receptors recruit and activate an adaptor protein called FADD (Fas-associated death domain), which in turn recruits and activates caspase-8, leading to the formation of the death-inducing signaling complex (DISC). 7,8 Once caspase-8 is activated, it can lead to apoptosis either by activating effector caspase-3 and -7, which in turn act on final death substrates, 8 or by activating Bid, which induces the accumulation of Bax in mitochondria, the release of cytochrome c from mitochondria, the activation of caspases-9, -3, and -7, and finally programmed cell death. 9,...

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“…Fas-induced apoptosis involves the activation of MKK6 and/or MKK3 by ICE-like protease, where MKK3/6 activates CPP32-like protease(s) to promote cell death and also activates p38 signaling pathway [40,41]. Anti-Fas antibody and interferon …”

Section: Discussionmentioning

confidence: 99%

Differential phosphorylation of mitogen-activated protein kinase families by epidermal growth factor and ultraviolet B irradiation in SV40-transformed human keratinocytes

Takahashi

Kinouchi

Manabe

et al. 2001

Journal of Dermatological Science

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ELSEVIER, Nakamura, S; Takahashi, H; Kinouchi, M; Manabe, A; Ishida-Yamamoto, A; Hashimoto, Y; Iizuka, H, JOURNAL OF DERMATOLOGICAL SCIENCE, 25(2), 139-149, 2001. authorSV-40 transformed human keratinocytes (SVHK cells) were stimulated with epidermal growth factor (EGF)2 and ultraviolet B (UVB) irradiation. Following the stimulation, cell growth, apoptosis, and the activities of mitogen-activated protein (MAP) kinase families were analyzed. EGF (100ng/ml) increased SVHK cell number compared with control cells cultured in serum-free DMEM medium. The EGF-stimulated cells did not show DNA fragmentation. In contrast, UVB irradiation (40mJ/cm2) markedly decreased viable cell number, that was accompanied with DNA fragmentation. EGF stimulated extracellular signal-regulated kinase (ERK) and stress-activated protein kinase/c-Jun N-terminal kinase (JNK). Following the EGF stimulation, phosphorylated ERK and JNK were detected by phospho-p42/44 MAP kinase antibody and phospho-SAPK/JNK antibody, respectively. On the other hand, UVB irradiation stimulated the phosphorylation of p38 and JNK but not of ERK. The stimulation of ERK and JNK induced by EGF was observed earlier than the stimulation of p38 and JNK induced by UVB. PD98059, a specific MAP kinase kinase (MAPKK) 1 (also referred to as MEK1) inhibitor, inhibited EGF-dependent cell proliferation, that was associated with the inhibition of ERK and JNK phosphorylation. In contrast, UVB-induced overall cell death was not significantly affected by PD98059, that inhibited phosphorylation of JNK but not of p38. PD98059, however, significantly augmented UVB-induced cell death earlier time points (30min - 2 h). These results indicate that ERK and JNK are activated following EGF stimulation, that might be associated with cell proliferation. On the other hand, UVB-induced apoptosis seems to be mostly associated with the activation of p38. JNK stimulation might provide an anti-apoptotic tonus during the UVB-induced, p38-associated SVHK cell death

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Apoptosis Signaling Pathway in T Cells Is Composed of ICE/Ced-3 Family Proteases and MAP Kinase Kinase 6b

Cited by 221 publications

References 65 publications

Mitochondrial Reactive Oxygen Species Mediate Cardiomyocyte Formation from Embryonic Stem Cells in High Glucose

Mitochondrial Reactive Oxygen Species Mediate Cardiomyocyte Formation from Embryonic Stem Cells in High Glucose

Lack of p38 MAP Kinase Activation in TRAIL-Resistant Cells is Not Related to the Resistance to TRAIL-Mediated Cell Death

Differential phosphorylation of mitogen-activated protein kinase families by epidermal growth factor and ultraviolet B irradiation in SV40-transformed human keratinocytes

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