Caspases determine the vulnerability of oligodendrocytes in the ischemic brain

Shibata, Mamoru; Hisahara, Shin; Hara, Hideaki; Yamawaki, Takemori; Fukuuchi, Yasuo; Yuan, Junying; Miura, Masayuki

doi:10.1172/jci10203

Cited by 84 publications

(88 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…34,35 The work described here provided further support for this hypothesis by demonstrating the critical role of caspase-11 in activating both caspase-3 and caspase-7 during LPS-induced shock. Furthermore, we established the temporal sequence of caspase-11, caspases-3/-7 and caspase-1 activation, and the independence of caspase-3 activation from that of cytokine secretion, at least in the early phase of LPS response.…”

Section: Discussionsupporting

confidence: 64%

“…C. Specificity of YVAD in the inhibition of caspase-1 but not caspase-11. 35 S-labeled in vitro translated substrates (*IL-1b for caspase-1 and *PARP for caspase-11) were incubated with recombinant caspase-1 (Casp-1) or caspase-11 (Casp-11). Increasing concentrations of pan-caspase inhibitor zVAD.fmk (zVAD) and caspase-1 inhibitor acYVAD.cmk (YVAD) were added (2, 10 and 20 mM where indicated) in the cleavage assay to examine the specificity of the inhibitor, ac.YVAD.cmk.…”

Section: Discussionmentioning

confidence: 99%

“…In vitro translation of 35 S-labeled proteins (IL-1b and PARP) was done using TNT-coupled transcription/translation kit (Promega, Madison, WI, USA). 35 S-labeled proteins were incubated with 1 mg of recombinant caspase-1 (pHZ2) or caspase-11 (pS15) 34 in 50 mM Tris-HCl (pH 8.0) buffer containing 0.5 mM EDTA, 0.5 mM sucrose, 10 mM DTT and protease inhibitor cocktails with or without peptide caspase inhibitor zVAD.fmk or ac.YVAD.cmk.…”

Section: In Vitro Cleavage Assaymentioning

confidence: 99%

“…Subsequently it was found that caspase-11 is required for the activation of caspase-3 in apoptosis induced by brain ischemia. 34,35 Furthermore, caspase-11-deficient oligodendrocytes are partially resistant to cell death induced by experimental autoimmune encephalomyelitis. 36 These studies suggest that caspase-11 plays a dual role in regulating both cytokine secretion and apoptosis.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Distinct downstream pathways of caspase-11 in regulating apoptosis and cytokine maturation during septic shock response

et al. 2002

View full text Add to dashboard Cite

Caspase-11 is an essential mediator of septic shock response and caspase-11-deficient mice are resistant to LPS-induced shock. Here we report that LPS-induced caspase-11 regulates lymphocyte apoptosis by activating both caspase-3 and caspase-7. The activation of caspase-11 preceded that of caspase-1 and caspases-3/-7, and in the absence of caspase-11, the activation of caspases-3/-7 was significantly reduced. The early activation of caspases-3/-7 by caspase-11 was not affected by blocking of caspase-1 activity and IL-1b release, implying that caspase-11 activates caspases-3/-7 independently of caspase-1 activation. Furthermore, we show that caspase-11-mediated apoptosis under septic condition is Bidindependent. Our work suggests that the human homologue of caspase-11 may be an effective therapeutic target for treatment of septic shock.

show abstract

Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Section: In Vitro Cleavage Assaymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Distinct downstream pathways of caspase-11 in regulating apoptosis and cytokine maturation during septic shock response

et al. 2002

View full text Add to dashboard Cite

show abstract

“…However, it has been demonstrated that intracellular apoptotic signals leading to a common endpoint, i.e., caspase-3 activation, occur in both neurons and glia following spinal cord injury (Emery et al, 1998;Hayashi et al, 1998;Springer et al, 1999;Beattie et al, 2000;Citron et al, 2000;Springer et al, 2000). Similar studies have documented evidence of caspase-3 activation in other types of CNS injury models, including head trauma and ischemia/stroke (Gottron et al, 1997;Hara et al, 1997;Yakovlev et al, 1997;Endres et al, 1998;Ni et al, 1998;Posmantur et al, 1998;Velier et al, 1999;Zhang et al, 1999;Clark et al, 2000;Eldadah and Faden, 2000;Shibata et al, 2000;Zhu et al, 2000). Numerous in vitro studies have demonstrated that caspase-3 activation is initiated, in part, by upstream events that result in the release of cytochrome c and Smac/DIABLO from the mitochondria (Liu et al, 1996;Bossy-Wetzel et al, 1998;Skulachev, 1998;Yang and Cortopassi 1998;Slee et al, 1999;Du et al, 2000;Verhagen et al, 2000).…”

Section: The Caspase-3 Apoptotic Cascadementioning

confidence: 96%

Apoptotic Cell Death Following Traumatic Injury to the Central Nervous System

Springer¹

2002

BMB Reports

View full text Add to dashboard Cite

Apoptotic cell death is a fundamental and highly regulated biological process in which a cell is instructed to actively participate in its own demise. This process of cellular suicide is activated by developmental and environmental cues and normally plays an essential role in eliminating superfluous, damaged, and senescent cells of many tissue types. In recent years, a number of experimental studies have provided evidence of widespread neuronal and glial apoptosis following injury to the central nervous system (CNS). These studies indicate that injury-induced apoptosis can be detected from hours to days following injury and may contribute to neurological dysfunction. Given these findings, understanding the biochemical signaling events controlling apoptosis is a first step towards developing therapeutic agents that target this cell death process. This review will focus on molecular cell death pathways that are responsible for generating the apoptotic phenotype. It will also summarize what is currently known about the apoptotic signals that are activated in the injured CNS, and what potential strategies might be pursued to reduce this cell death process as a means to promote functional recovery.

show abstract

Baculovirus P35 protein: An overview of its applications across multiple therapeutic and biotechnological arenas

Sahdev¹,

Saini²,

Hasnain

2009

Biotechnology Progress

View full text Add to dashboard Cite

Baculovirus immediate early P35 protein is well known for its anti-apoptotic as well as anti-oxidant properties. Mechanism of action of P35 involves inhibition of a vast range of initiator to executioner class of caspases. In addition, P35's role in inhibiting oxidant-induced mitochondrial damage, primarily in the apoptotic pathway, has also been extensively investigated. Elucidation of P35's functions during regulation of programmed cell death (PCD) has led to a renewed focus on exploiting this basic knowledge for clinical and other related applications. This review outlines specific biochemical and genetic pathways where P35 intervenes and regulates rate-limiting steps in the apoptotic signaling cascade. Research efforts are underway to utilize P35 as an agent in regulating apoptosis and under certain circumstances, also explore the therapeutic potential of its anti-oxidant features. One of the major outcomes of recent studies include significantly improved effectiveness of cytochrome P450 directed enzyme pro-drug delivery tools when used in conjunction with P35, which may help in alleviating drug resistance in tumor cells and simultaneously prolonging the cytotoxic effects of anti-cancer drugs. Moreover, applied research carried out recently in the fields of diabetes, ischemia-induced neuronal cell death, experimental autoimmune encephalomyelitis (EAE), multiple sclerosis (MS), inflammatory arthritis, cardiovascular and ocular disorders illustrate P35's utilization across diverse therapeutic areas and will certainly make it an attractive biomolecule for the discovery research.

show abstract

Caspases determine the vulnerability of oligodendrocytes in the ischemic brain

Cited by 84 publications

References 49 publications

Distinct downstream pathways of caspase-11 in regulating apoptosis and cytokine maturation during septic shock response

Distinct downstream pathways of caspase-11 in regulating apoptosis and cytokine maturation during septic shock response

Apoptotic Cell Death Following Traumatic Injury to the Central Nervous System

Baculovirus P35 protein: An overview of its applications across multiple therapeutic and biotechnological arenas

Contact Info

Product

Resources

About