Gsdma3 is a new factor needed for TNF-α-mediated apoptosis signal pathway in mouse skin keratinocytes

Lei, Mingxing; Bai, Xiufeng; Yang, Tian; Lai, Xiangdong; Qiu, Weiming; Yang, Li; Lian, Xiaohua

doi:10.1007/s00418-012-0960-1

Cited by 46 publications

(32 citation statements)

References 29 publications

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“…TNF-α induces caspase 3 activation which leads to subsequent cellular damage including endothelial barrier dysfunction [29, 30]. We first assessed whether HDAC6 inhibition can block caspase-3 activation in lung endothelial cells.…”

Section: Resultsmentioning

confidence: 99%

HDAC6 inhibition prevents TNF-α-induced caspase 3 activation in lung endothelial cell and maintains cell-cell junctions

et al. 2016

Oncotarget

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Pro-inflammatory mediators such as TNF-α induce caspase activation in endothelial cells, which leads to degradation of cellular proteins, induction of apoptotic signaling, and endothelial cell dysfunction. New therapeutic agents that can inhibit caspase activation may provide protection against inflammatory injury to endothelial cells. In the present study, we examined the effects of selective histone deacetylase 6 (HDAC6) inhibition on TNF-α induced caspase 3 activation and cell-cell junction dysfunction in lung endothelial cells. We also assessed the protective effects of HDAC6 inhibition against lung inflammatory injury in a mouse model of endotoxemia. We demonstrated that selective HDAC6 inhibition or knockdown of HDAC6 expression was able to prevent caspase 3 activation in lung endothelial cells and maintain lung endothelial cell-cell junctions. Mice pre-treated with HDAC6 inhibitors exhibited decreased endotoxin-induced caspase 3 activation and reduced lung vascular injury as indicated by the retention of cell-cell junction protein VE-Cadherin level and alleviated lung edema. Collectively, our data suggest that HDAC6 inhibition is a potent therapeutic strategy against inflammatory injury to endothelial cells.

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Section: Resultsmentioning

confidence: 99%

HDAC6 inhibition prevents TNF-α-induced caspase 3 activation in lung endothelial cell and maintains cell-cell junctions

et al. 2016

Oncotarget

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“…They share similar phenotypes, including cicatricial alopecia accompanied by hair follicle differentiation defects, atrophy of the stratum granulosum (SG) and hyperkeratosis [17][18][19][20][21][22][23]. Previous reports suggest that Gsdma3 is associated with hair follicle development [21,24], tumour necrosis factor (TNF)α-induced apoptosis [25], skin inflammation [26,27] and immune-mediated destruction of bulge stem cells [23]. However, the physiological function of Gsdma3 is still unclear.…”

Section: Introductionmentioning

confidence: 97%

Loss of conserved Gsdma3 self-regulation causes autophagy and cell death

Shi

Tang

et al. 2015

Biochemical Journal

101

106

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Gasdermin A3 (Gsdma3) was originally identified in association with hair-loss phenotype in mouse mutants. Our previous study found that AE mutant mice, with a Y344H substitution at the C-terminal domain of Gsdma3, display inflammation-dependent alopecia and excoriation [Zhou et al. (2012) Am. J. Pathol. 180, 763-774]. Interestingly, we found that the newly-generated null mutant of Gsdma3 mice did not display the skin dysmorphology, indicating that Gsdma3 is not essential for differentiation of epidermal cells and maintenance of the hair cycle in normal physiological conditions. Consistently, human embryonic kidney (HEK)293 and HaCaT cells transfected with wild-type (WT) Gsdma3 did not show abnormal morphology. However, Gsdma3 Y344H mutation induced autophagy. Gsdma3 N-terminal domain, but not the C-terminal domain, also displayed the similar pro-autophagic activity. The Gsdma3 Y344H mutant protein and N-terminal domain-induced autophagy was associated with mitochondria and ROS generation. Co-expression of C-terminal domain reversed the cell autophagy induced by N-terminal domain. Moreover, C-terminal domain could be co-precipitated with N-terminal domain. These data indicated that the potential pro-autophagic activity of WT Gsdma3 protein is suppressed through an intramolecular inhibition mechanism. Studies on other members of the GSDM family suggested this mechanism is conserved in several sub-families.

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“…Qin et al have reported that inhibition of cell apoptosis significantly improves heart function in myocardial infarction rabbits [12]. In particular, TNF- α /caspase-3-mediated apoptosis is considered the main apoptotic pathway in heart failure (HF) [13]. Therefore, in vivo detection of apoptosis may not only prove clinically useful in diagnosis and prognosis but also indicate that the TNF- α /caspase-3 pathway is potential therapeutic target [14].…”

Section: Introductionmentioning

confidence: 99%

Time‐Course of the Effects of QSYQ in Promoting Heart Function in Ameroid Constrictor‐Induced Myocardial Ischemia Pigs

Qiu

Yang

Xiao

et al. 2014

Evidence-Based Complementary and Alternative Medicine

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We aim to investigate the therapeutic effects of QSYQ on a pig myocardial ischemia (MI) model and to determine its mechanism of action. The MI model was induced by Ameroid constriction of the left anterior descending coronary (LAD) in Ba-Ma miniature pigs. Four groups were created: model group, digoxin group, QSYQ group, and sham-operated group. Heart function, Ang II, CGMP, TXB2, BNP, and cTnT were evaluated before (3 weeks after operation: 0 weeks) and at 2, 4, and 8 weeks after drug administration. After 8 weeks of administration, the pigs were sacrificed for cardiac injury measurements. Pigs with MI showed obvious histological changes, including BNP, cTnT, Ang II, CGRP, TXB2, and ET, deregulated heart function, and increased levels of apoptotic cells in myocardial tissue. Treatment with QSYQ improved cardiac remodeling by counteracting those events. The administration of QSYQ was accompanied by a restoration of heart function and of the levels of Ang II, CGRP, TXB2, ET BNP, and cTnT. In addition, QSYQ attenuated administration, reduced the apoptosis, and decreased the level of TNF-α and active caspase-3. In conclusion, administration of QSYQ could attenuate Ameroid constrictor induced myocardial ischemia, and TNF-α and active caspase-3 seemed to be the critical potential target of QSYQ.

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Gsdma3 is a new factor needed for TNF-α-mediated apoptosis signal pathway in mouse skin keratinocytes

Cited by 46 publications

References 29 publications

HDAC6 inhibition prevents TNF-α-induced caspase 3 activation in lung endothelial cell and maintains cell-cell junctions

HDAC6 inhibition prevents TNF-α-induced caspase 3 activation in lung endothelial cell and maintains cell-cell junctions

Loss of conserved Gsdma3 self-regulation causes autophagy and cell death

Time‐Course of the Effects of QSYQ in Promoting Heart Function in Ameroid Constrictor‐Induced Myocardial Ischemia Pigs

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