Fundamental role of the Rip2/caspase-1 pathway in hypoxia and ischemia-induced neuronal cell death

Zhang, Wenhua; Wang, Xin; Narayanan, Malini; Zhang, Yu; Huo, Chunfeng; Reed, John C.; Friedlander, Robert M.

doi:10.1073/pnas.2534856100

Cited by 186 publications

(195 citation statements)

References 29 publications

Supporting

Mentioning

179

Contrasting

Unclassified

Order By: Relevance

“…Our previous results, and the results published here, are in clear contrast to the detrimental effects of caspase 1 in more severe ischemia/reperfusion injury models in heart and kidney, which leave many cells anoxic rather than hypoxic and severely limit the initiation of adaptive survival responses. In these cases caspase 1-mediated inflammation is detrimental (33,34). Our findings, although initially surprising, are consistent with our understanding of caspase 1-mediated regulation of adaptive responses in non-myeloid cell types.…”

Section: Discussionsupporting

confidence: 88%

Caspase 1 Activation Is Protective against Hepatocyte Cell Death by Up-regulating Beclin 1 Protein and Mitochondrial Autophagy in the Setting of Redox Stress

Sun¹,

Gao²,

Loughran

et al. 2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background:The role of caspase 1 in non-immune cells that do not express IL1␤/IL18, like hepatocytes, is largely unknown. Results: Caspase 1 activation limits excessive mitochondrial reactive oxygen species during oxidative stress by up-regulating beclin1 and mitochondrial clearance in hepatocytes. Conclusion: Caspase 1 is hepatoprotective after oxidative stress. Significance: Our findings suggest a novel role for caspase 1 activation in promoting adaptive responses to oxidative stress.

show abstract

Section: Discussionsupporting

confidence: 88%

Caspase 1 Activation Is Protective against Hepatocyte Cell Death by Up-regulating Beclin 1 Protein and Mitochondrial Autophagy in the Setting of Redox Stress

Sun¹,

Gao²,

Loughran

et al. 2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…20,[23][24][25] On the other hand, significant evidence from studies using Csp-1 inhibitors, a Csp-1 DN construct and Csp-1 null cells indicates that Csp-1 can be involved in cell death. [26][27][28][29] The increase of Csp-1 in AD raises the possibility that Csp-1 also activates Csp-6 in vivo. Unfortunately, despite serious attempts, we were unable to show the active subunits of Csp-1 in AD tissues.…”

Section: Discussionmentioning

confidence: 99%

Caspase-1 activation of caspase-6 in human apoptotic neurons

et al. 2005

View full text Add to dashboard Cite

Active caspase-6 (Csp-6) induces cell death in primary cultures of human neurons and is abundant in the neuropathological lesions of Alzheimer's disease. However, the mode of Csp-6 activation is not known. Here, we show that the Csp-1 inhibitor, Z-YVAD-fmk specifically prevents activation of Csp-6 and cell death in human neurons. A transient increase in Csp-1-like activity and an increase in the p23Csp-1 subunit occur early after serum deprivation. Recombinant active Csp-1 (R-Csp-1) cleaves recombinant and neuronal pro-Csp-6 in vitro resulting in Csp-6 activity. However, R-Csp-1 does not induce cell death when microinjected in human neurons despite the inhibition of serum-deprivation induced cell death with a Csp-1 dominant negative construct. These results show that Csp-1 is an upstream positive regulator of Csp-6-mediated cell death in primary human neurons. Furthermore, these results suggest that the activation of Csp-1 must be accompanied by an apoptotic insult to induce Csp-6-mediated cell death.

show abstract

“…Also, Rho GDP dissociation inhibitor ␥ (also known as RIP2) was significantly down-regulated in peak EAE. RIP2 is a stress-inducible upstream modulator of procaspase-1 apoptotic activation and its decreased expression may reflect an active mechanism to reduce neuronal cell death (35). In addition, caspase-1 is an activator of IL-1b and a reduced expression might contribute to a negative regulation of the inflammatory process (36).…”

Section: Discussionmentioning

confidence: 99%

Modular Transcriptional Activity Characterizes the Initiation and Progression of Autoimmune Encephalomyelitis

Baranzini

Bernard

Oksenberg

2005

The Journal of Immunology

View full text Add to dashboard Cite

Murine experimental autoimmune encephalomyelitis is a well-established model that recapitulates many clinical and physiopathological aspects of multiple sclerosis (MS). An important conceptual development in the understanding of both experimental autoimmune encephalomyelitis and MS pathogenesis has been the compartmentalization of the mechanistic process into two distinct but overlapping and connected phases, inflammatory and neurodegenerative. However, the dynamics of CNS transcriptional changes that underlie the development and regression of the phenotype are not well understood. Our report presents the first high frequency longitudinal study looking at the earliest transcriptional changes in the CNS of NOD mice immunized with myelin oligodendrocyte glycoprotein 35-55 in CFA. Microarray-based gene expression profiling and histopathological analysis were performed from spinal cord samples obtained at 13 time points around the first clinical symptom (every other day until day 11 and every day onward until day 19 postimmunization). Advanced statistics and data-mining algorithms were used to identify expression signatures that correlated with disease stage and histological profiles. Discrete phases of neuroinflammation were accompanied by distinctive expression signatures, in which altered immune to neural gene expression ratios were observed. By using high frequency gene expression analysis we captured expression profiles that were characteristic of the transition from innate to adaptive immune response in this experimental paradigm between days 11 and 12 postimmunization. Our study demonstrates the utility of large-scale transcriptional studies and advanced data mining to decipher complex biological processes such as those involved in MS and other neurodegenerative disoders. The Journal of Immunology, 2005, 174: 7412-7422.C hronic autoimmune diseases like multiple sclerosis (MS) 3 develop over the course of months or years without exhibiting any observable phenotype. By following patterns of gene expression over time in suitable and well-controlled experimental models, it should be possible to identify early pathogenic mechanisms that precede symptoms and to unravel regulatory events undetectable at the clinical or pathological level. Experimental autoimmune encephalomyelitis (EAE) can be induced in a variety of animal species, including nonhuman primates, by active immunization with myelin proteins or their peptide derivatives, as well as by adoptive transfer of activated CD4 ϩ T cells specific for myelin components (1-6). The encephalitogenic challenge compromises blood-brain barrier (BBB) integrity and produces CNS inflammation and neurodegeneration leading to neurologic disease. Ataxia and paralysis occurs first in the tail and hind limbs, and progressive deterioration later affects the forelimbs, eventually causing death. From all available EAE murine models, the one induced by myelin oligodendrocyte glycoprotein (MOG) in the NOD background is perhaps the most adequate for a time-controlled experiment, in ...

show abstract

Fundamental role of the Rip2/caspase-1 pathway in hypoxia and ischemia-induced neuronal cell death

Cited by 186 publications

References 29 publications

Caspase 1 Activation Is Protective against Hepatocyte Cell Death by Up-regulating Beclin 1 Protein and Mitochondrial Autophagy in the Setting of Redox Stress

Caspase 1 Activation Is Protective against Hepatocyte Cell Death by Up-regulating Beclin 1 Protein and Mitochondrial Autophagy in the Setting of Redox Stress

Caspase-1 activation of caspase-6 in human apoptotic neurons

Modular Transcriptional Activity Characterizes the Initiation and Progression of Autoimmune Encephalomyelitis

Contact Info

Product

Resources

About