Immunohistochemical detection of Bax and Bcl-2 proteins in gerbil hippocampus following transient forebrain ischemia

Hara, Akira; Iwai, Tomohiko; Niwa, Masayuki; Uematsu, Toshihiko; Yoshimi, Naoki; Tanaka, Takuji; Mori, Hideki

doi:10.1016/0006-8993(95)01436-5

Cited by 98 publications

(39 citation statements)

References 13 publications

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“…Increases in Bax are found specifically in neurons that undergo cell death in ischemia-sensitive regions of the brain such as the CA1 sector of the hippocampus, in rat, hamster, and dog models of global cerebral ischemia. [26][27][28] Bax protein and mRNA levels also rapidly increase in neurons within the penumbra region of focal infarcts, in rodent models of middle cerebral artery occlusion. 29 Moreover, evidence suggesting a cause-and-effect relation between increases in Bax expression and ischemia-associated neuronal cell death has come from experiments using baxÀ/À mice generated by Korsmeyer et al 30 Elevations in Bax protein and mRNA levels were described in neurons in vivo after excitotoxic lesion with the N-methyl-D-aspartate receptor agonist, quinolinic acid, 31 as well as after systemic administration of kainic acid.…”

Section: Introductionmentioning

confidence: 99%

Proapoptotic multidomain Bcl-2/Bax-family proteins: mechanisms, physiological roles, and therapeutic opportunities

2006

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Bcl-2-family proteins are central regulators of cell life and death. At least three major classes of Bcl-2-family proteins have been delineated, including proapoptotic proteins that contain several conserved regions of sequence similarity (termed 'multidomain'). In mammals, the multidomain proteins (MDPs) of the Bcl-2 family include Bax, Bak, and Bok. The founding member of the MDP group of Bcl-2-family proteins was discovered by Stanley Korsmeyer and co-workers, initiating an exciting area of cell death research. The status of current knowledge about the mechanisms and functions of MDPs is reviewed here, and some areas for future research are outlined. Therapeutic opportunities emerging from a growing understanding of MDPs with respect to their threedimensional structures, biochemical actions, and roles in disease raise hopes that the foundation of basic research laid by Korsmeyer and others will eventually be translated into clinical benefits, leaving a legacy that benefits the world for many decades.

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Section: Introductionmentioning

confidence: 99%

Proapoptotic multidomain Bcl-2/Bax-family proteins: mechanisms, physiological roles, and therapeutic opportunities

2006

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“…In response to these stimuli, a cascade of proteolytic enzymes known as caspases and other proteins such as B-cell lymphoma-leukemia 2 (Bcl2)-associated X protein (Bax) and transformation related protein 53 (Trp53) as well as antiapoptotic proteins including Bcl2 and inhibitor of apoptosis protein (Iap), are activated. [71][72][73][74] Therefore, inhibition of apoptotic gene expression and stimulation of antiapoptotic proteins may offer a vascular protection strategy. In addition to its angiogenic and antiproliferative effects as described above, VEGF also stimulates endothelial cell survival.…”

Section: Chronicmentioning

confidence: 99%

Targets for Vascular Protection After Acute Ischemic Stroke

Fagan

Hess²,

Hohnadel³

et al. 2004

Stroke

229

165

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Background— Vascular damage caused by cerebral ischemia leads to edema, hemorrhage formation, and worsened outcomes in ischemic stroke patients. Therapeutic interventions need to be developed to provide vascular protection. The purpose of this review is to identify the pathophysiologic processes involved in vascular damage after ischemia, which may lead to strategies to provide vascular protection in ischemic stroke patients. Summary of Comment— The pathologic processes caused by vascular injury after an occlusion of a cerebral artery can be separated into acute (hours), subacute (hours to days), and chronic (days to months). Targets for intervention can be identified for all 3 stages. Acutely, superoxide is the predominant mediator, followed by inflammatory mediators and proteases subacutely. In the chronic phase, proapoptotic gene products have been implicated. Conclusions— Pharmacological agents designed to target specific pathologic and protective processes affecting the vasculature should be used in clinical trials of vascular protection after acute ischemic stroke.

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“…The inability of affected neurons to synthesize new proteins has far-reaching consequences, because such neurons cannot react to the severe form of stress elicited by transient ischemia with an up-regulation of the expression of stress genes coding for neuroprotective proteins like HSP70 or Bcl-2. Transcription of various stress genes is indeed markedly activated after ischemia (10), but the respective proteins are not synthesized (10)(11)(12)(13). Experiments on the stable neuroblastoma cell line SH-SY5Y (14) showed that transcription and translation of the E3 ubiquitin ligase parkin is considerably up-regulated under conditions associated with ER dysfunction.…”

mentioning

confidence: 99%

Down-regulation of parkin protein in transient focal cerebral ischemia: A link between stroke and degenerative disease?

Mengesdorf

Jensen

Mies

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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Ubiquitylated protein aggregates are characteristic features of neurodegenerative disorders that are also found in acute pathological states of the brain such as stroke. Many of the proteins connected to neurodegenerative diseases play a role in the ubiquitin-proteasomal pathway. Mutation of one of these proteins, the E3 ubiquitin ligase parkin, is the cause of autosomal recessive juvenile Parkinson's disease. Here we show that transient focal cerebral ischemia of 1-h duration induces marked depletion of parkin protein levels, to 60%, 36%, 33%, and 25% of controls after 1, 3, 6, and 24 h of reperfusion, but that ischemia does not cause lower protein levels of E2 ubiquitin-conjugating enzymes Ubc6, Ubc7, or Ubc9. After 3 h of reperfusion, when parkin protein levels were already reduced to <40% of control, ATP levels were almost completely recovered from ischemia and we did not observe DNA fragmentation, suggesting that parkin depletion preceded development of neuronal cell death. Up-regulation of the expression of parkin has been shown to protect cells from injury induced by endoplasmic reticulum (ER) dysfunction, and this form of cellular stress is also triggered by transient cerebral ischemia. However, in contrast to observations in neuroblastoma cells, we saw no upregulation of parkin expression in primary neuronal cell cultures after induction of ER dysfunction. Our data thus suggest that ischemia-induced depletion of parkin protein may contribute to the pathological process resulting in cell injury by increasing the sensitivity of neurons to ER dysfunction and the aggregation of ubiquitylated proteins during the reperfusion period.

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Immunohistochemical detection of Bax and Bcl-2 proteins in gerbil hippocampus following transient forebrain ischemia

Cited by 98 publications

References 13 publications

Proapoptotic multidomain Bcl-2/Bax-family proteins: mechanisms, physiological roles, and therapeutic opportunities

Proapoptotic multidomain Bcl-2/Bax-family proteins: mechanisms, physiological roles, and therapeutic opportunities

Targets for Vascular Protection After Acute Ischemic Stroke

Down-regulation of parkin protein in transient focal cerebral ischemia: A link between stroke and degenerative disease?

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