The Role of Protein Kinase C in Cerebral Ischemic and Reperfusion Injury

Bright, Rachel; Mochly‐Rosen, Daria

doi:10.1161/01.str.0000189996.71237.f7

Cited by 188 publications

(152 citation statements)

References 115 publications

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“…In the brain and spinal cord, PKCα, PKCβ1, PKCβ2, PKCγ, PKCε, PKCδ, PKCη, PKCθ, and PKCξ mRNA and protein are present and demonstrate unique tissue, cellular, and subcellular localizations. Previous reports suggest that ischemic preconditioning enhances downregulation of cell signaling mediated by PKCγ, normalization of calcium homeostasis, and activation of PKCδ and ε [39] . Recent data demonstrate the key role of the PKCε signaling pathway in the context of ischemic preconditioning.…”

Section: Intracellular Survival Signals and Neuroprotectionmentioning

confidence: 94%

The neuroprotective mechanism of brain ischemic preconditioning

2009

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Brain ischemia is one of the most common causes of death and the leading cause of adult disability in the world. Brain ischemic preconditioning (BIP) refers to a transient, sublethal ischemia which results in tolerance to later, otherwise lethal, cerebral ischemia. Many attempts have been made to understand the molecular and cellular mechanisms underlying the neuroprotection offered by ischemic preconditioning. Many studies have shown that neuroprotective mechanisms may involve a series of molecular regulatory pathways including activation of the N-methyl-D-aspartate (NMDA) and adenosine receptors; activation of intracellular signaling pathways such as mitogen activated protein kinases (MAPK) and other protein kinases; upregulation of Bcl-2 and heat shock proteins (HSPs); and activation of the ubiquitin-proteasome pathway and the autophagic-lysosomal pathway. A better understanding of the processes that lead to cell death after stroke as well as of the endogenous neuroprotective mechanisms by which BIP protects against brain ischemic insults could help to develop new therapeutic strategies for this devastating neurological disease. The purpose of the present review is to summarize the neuroprotective mechanisms of BIP and to discuss the possibility of mimicking ischemic preconditioning as a new strategy for preventive treatment of ischemia.

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Section: Intracellular Survival Signals and Neuroprotectionmentioning

confidence: 94%

The neuroprotective mechanism of brain ischemic preconditioning

2009

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“…Furthermore, by decreasing PKCγ expression with antisense oligonucleotides, the insulin induced protection from insult was abolished [63]. For a comprehensive review of PKCs in cerebral ischemia, see [61,64].…”

Section: Pkcγ and Pkcε In Neural Tissuesmentioning

confidence: 99%

Protein kinase C as a stress sensor

Barnett

Madgwick

Takemoto

2007

Cellular Signalling

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While there are many reviews which examine the group of proteins known as protein kinase C (PKC), the focus of this article is to examine the cellular roles of two PKCs that are important for stress responses in neurological tissues (PKCγ and ε) and in cardiac tissues (PKCε). These two kinases, in particular, seem to have overlapping functions and interact with an identical target, connexin 43 (Cx43), a gap junction protein which is central to proper control of signals in both tissues. While PKCγ and PKCε both help protect neural tissue from ischemia, PKCε is the primary PKC isoform responsible for responding to decreased oxygen, or ischemia, in the heart. Both do this through Cx43.It is clear that both PKCγ and PKCε are necessary for protection from ischemia. However, the importance of these kinases has been inferred from preconditioning experiments which demonstrate that brief periods of hypoxia protect neurological and cardiac tissues from future insults, and that this depends on the activation, translocation, or ability for PKCγ and/or PKCε to interact with distinct cellular targets, especially Cx43.This review summarizes the recent findings which define the roles of PKCγ and PKCε in cardiac and neurological functions and their relationships to ischemia/reperfusion injury. In addition, a biochemical comparison of PKC γ and PKC ε and a proposed argument for why both forms are present in neurological tissue while only PKC ε is present in heart, are discussed. Finally, the biochemistry of PKCs and future directions for the field are discussed, in light of this new information.

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“…PKC is a lipid activated serine/threonine kinase and has been known to have both antiapoptotic and proapoptotic functions depending on its isoforms (Webb et al 2000;Bright and Mochly-Rosen 2005). Certain PKC isoforms can promote cell survival by directly phosphorylating Raf-1 without Ras activation and leading to activate Raf/MEK/Erk pathways (Kolch et al 1993;Huang et al 1995;McCubrey et al 2000;Oliva et al 2005).…”

Section: Journal Of the Association For Research In Otolaryngologymentioning

confidence: 99%

“…This molecule recruits protein kinase B (PKB, also called Akt) and phosphoinositide-dependent kinase 1 (PDK-1). PDK-1 phosphorylates and activates PKC isoforms (Huang et al 1995;Balendran et al 2000;Webb et al 2000;Cantley 2002;Kuemmerle 2003;Bright and Mochly-Rosen 2005). Protein kinase B (Akt) is the common downstream target of PI3K.…”

Section: Journal Of the Association For Research In Otolaryngologymentioning

confidence: 99%