Cardiac Muscle Cell Hypertrophy and Apoptosis Induced by Distinct Members of the p38 Mitogen-activated Protein Kinase Family

Wang, Yibin; Huang, Shuang; Sah, Valerie P.; Ross, John; Brown, Joan Heller; Han, Jiahuai; Chien, Kenneth R.

doi:10.1074/jbc.273.4.2161

Cited by 791 publications

(672 citation statements)

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“…In cardiac myocytes, expression of activated forms of MKK3 and MKK6 led to different responses; active MKK3 caused apoptosis while active MKK6 invoked hypertrophy. 36 Studies with MKK3 À/À and MKK6 À/À mice also revealed distinct functions of these MKKs in immune responses. 37 The lack of inhibitory effect of MKK3-DN on Oc differentiation in spite of the decrease in NFATc1 induction by RANKL (Figures 5d and 6b) is puzzling in view of the reports that suggested NFATc1 as a key regulator of osteoclastogenesis.…”

Section: Discussionmentioning

confidence: 99%

Osteoclast differentiation requires TAK1 and MKK6 for NFATc1 induction and NF-κB transactivation by RANKL

et al. 2006

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Osteoclast (Oc) differentiation is fundamentally controlled by receptor activator of nuclear factor kappaB ligand (RANKL). RANKL signalling targets include mitogen-activated protein kinases (MAPKs), nuclear factor kappaB (NF-jB), and nuclear factor of activated T cells (NFAT)c1. In this study, we found that p38 MAPK upstream components transforming growth factor-beta-activated kinase 1 (TAK1), MKK3, and MKK6 increased by RANKL in an early stage of osteoclastogenesis from primary bone marrow cells, which led to enhanced p38 activation. Retroviral transduction of dominant-negative (DN) forms of TAK1 and MKK6, but not that of MKK3, reduced Oc differentiation. Transduction of TAK1-DN and MKK6-DN and treatment with the p38 inhibitor SB203580 attenuated NFATc1 induction by RANKL. TAK1-DN, MKK6-DN, and SB203580, but not MKK3-DN, also suppressed RANKL stimulation of NF-jB transcription activity in a manner dependent on p65 phosphorylation on Ser-536. These results indicate that TAK1 and MKK6 constitute the p38 signalling pathway to participate to Oc differentiation by RANKL through p65 phosphorylation and NFATc1 induction, and that MKK6 and MKK3 have differential roles in osteoclastogenesis from bone marrow precursors.

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Section: Discussionmentioning

confidence: 99%

Osteoclast differentiation requires TAK1 and MKK6 for NFATc1 induction and NF-κB transactivation by RANKL

et al. 2006

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“…Recombinant adenoviruses (Ad) expressing activated MKK3bE, MKK6bE, green fluorescent protein (GFP) and dominant negative p38 MAP kinase α driven by a cytomegalovirus promoter (Ad/MKK3bE, Ad/MKK6bE Ad/CMV-GFP and Ad/ p38αdn), respectively have been described previously. 29,30 Cell Viability Assay. Cells were seeded in the same medium on 96-well plates at densities of 1 x 10 4 /well and held at 37˚C for 1 day before treatment with TRAIL protein (R & D Systems, Inc. Minneapolis, MN), anisomycin (Calbiochem, San Diego, CA), or adenovectors.…”

Section: Methodsmentioning

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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“…the p38 MAPK, play a pivotal role in the development of heart failure, including diabetic cardiomyopathy [10]. Via its signalling cascade, the p38 MAPK modulates genes that regulate myocyte apoptosis, cellular hypertrophy, cardiac fibrosis, and cardiac cytokine-mediated inflammation [11][12][13]. Because the p38 MAPK is not only upregulated and phosphorylated by ischaemia [14], but also, for example, by angiotensin II [15], oxidative stress [16], and high glucose levels [10], inhibition of p38 MAPK could be a potent new therapeutic option for treatment of diabetic cardiomyopathy.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of p38 mitogen-activated protein kinase attenuates left ventricular dysfunction by mediating pro-inflammatory cardiac cytokine levels in a mouse model of diabetes mellitus

et al. 2006

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Aims/hypothesis We investigated the effect of SB 203580, a pharmacological inhibitor of p38 mitogen-activated protein kinase (MAPK), on cardiac inflammation, cardiac fibrosis, and left ventricular function using an animal model of diabetic cardiomyopathy. Materials and methods Diabetes mellitus was induced by streptozotocin (50 mg/kg i.p. for 5 days) in 20 C57/BL6J mice. Diabetic mice were treated daily with the p38 MAPK inhibitor SB 203580 (1 mg/kg daily, n=10) or with placebo (n=10) and were compared to non-diabetic controls. Left ventricular function was measured by pressure-volume loops after 8 weeks of diabetes mellitus. The parameters for systolic function were the end systolic pressure-volume relationship (ESPVR) and the left ventricular end systolic pressure. The parameters for diastolic function were the left ventricular end diastolic pressure and the end diastolic pressure-volume relationship (EDPVR). Cardiac tissue was analysed by ELISA for the protein content of the cytokines TNF-α, IL6, IL1-β, and TGF-β1. Phosphorylation of MAPK p38 was analysed by western blot, and the total cardiac collagen content was analysed by Sirius red staining.

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Cardiac Muscle Cell Hypertrophy and Apoptosis Induced by Distinct Members of the p38 Mitogen-activated Protein Kinase Family

Cited by 791 publications

References 51 publications

Osteoclast differentiation requires TAK1 and MKK6 for NFATc1 induction and NF-κB transactivation by RANKL

Osteoclast differentiation requires TAK1 and MKK6 for NFATc1 induction and NF-κB transactivation by RANKL

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

Inhibition of p38 mitogen-activated protein kinase attenuates left ventricular dysfunction by mediating pro-inflammatory cardiac cytokine levels in a mouse model of diabetes mellitus

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