Protein Kinase C Isozymes in Stroke

Chou, Wen Hai; Messing, Robert O.

doi:10.1016/j.tcm.2005.01.003

Cited by 65 publications

(60 citation statements)

References 33 publications

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“…Instead of intervening in the pathological process that already has occurred in the ischemic brain (25,26), we used bryostatin-1 (21,27), a potent PKC activator with an antitumorigenic pharmacologic profile, in an attempt to boost neurorepair activity and synaptogenesis pharmacologically. Bryostatin-1, which crosses the blood-brain barrier when administered peripherally (28), produces a relatively selective activation of the PKC isozyme, which is neuroprotective (29)(30)(31) and has a lower median effective dose than PKC␦ for bryostatin-1 in its translocation (thus activation), whereas PKC␦ is most likely involved in ischemic injury during ischemia-reperfusion (32)(33)(34). We recently showed that PKC activation with bryostatin-1 enhanced exactly those synaptogenesis, presynaptic/postsynaptic ultrastructural specialization, and protein synthesis functions involved in rat maze learning and memory (20,35).…”

Section: Resultsmentioning

confidence: 99%

Poststroke neuronal rescue and synaptogenesis mediated in vivo by protein kinase C in adult brains

Sun

Hongpaisan

Nelson

et al. 2008

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

114

103

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Global cerebral ischemia/hypoxia, as can occur during human stroke, damages brain neural networks and synaptic functions. The recently demonstrated protein kinase C (PKC) activation-induced synaptogenesis in rat hippocampus suggested the potential of PKC-mediated antiapoptosis and synaptogenesis during conditions of neurodegeneration. Consequently, we examined the effects of chronic bryostatin-1, a PKC activator, on the cerebral ischemia/hypoxia-induced impairment of synapses and neurotrophic activity in the hippocampal CA1 area and on hippocampus-dependent spatial learning and memory. Postischemic/hypoxic bryostatin-1 treatment effectively rescued ischemia-induced deficits in synaptogenesis, neurotrophic activity, and spatial learning and memory. These results highlight a neuroprotective signaling pathway, as well as a therapeutic strategy with an extended time window for reducing brain damage due to stroke by activating particular PKC isozymes.bryostatin ͉ ischemia ͉ neuroprotection ͉ protein kinase C ͉ rat T emporary or permanent restriction of cerebral blood flow and oxygen supply results in cerebral ischemia and ischemic stroke, the third-leading cause of death and the most common cause of long-term disability in developed countries. Thrombolytic therapy (eg, recombinant tissue plasminogen activator) to achieve early arterial recanalization is the only option currently available to treat ischemic stroke. But this therapy's time-dependent effect (within 3 h after the event) limits its clinical use to only 5% of candidate patients (1), and it carries an increased risk of intracranial hemorrhage, reperfusion injury, and diminishing cerebral artery reactivity (2-5). Neuronal death and injury after cerebral ischemia involve pathological changes associated with necrosis and delayed apoptosis (6, 7). Neurons in the infarction core of focal, severe stroke are immediately eliminated and cannot be saved once ischemia develops. The ischemic penumbra, (i.e, brain tissues surrounding the core in focal ischemic stroke) and the sensitive neurons/networks in global cerebral ischemia are still sustained by the diminished blood supply, however. Further damage in these ischemic brain tissues occurs in a delayed manner after cerebral ischemia/stroke (8-10), responsible for clinical deterioration. Thus, effective postischemic therapy with an extended time window remains one of the greatest challenges to modern medical practice.A consistent consequence of cerebral ischemia/hypoxia in humans and other mammals is central nervous system dysfunction, the nature of which depends on the location and extent of injury. It has been well established that global cerebral ischemia/hypoxia selectively injures or damages the pyramidal neurons in the dorsal hippocampal CA1 area (11-14), which are essential for episodic memory, providing a sensitive measure for monitoring ischemic damage and recovery functionally. Experimental cerebral ischemia is usually induced focally through, for example, occlusion of the middle cerebral artery, or globally...

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Section: Resultsmentioning

confidence: 99%

Poststroke neuronal rescue and synaptogenesis mediated in vivo by protein kinase C in adult brains

Sun

Hongpaisan

Nelson

et al. 2008

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

114

103

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“…These tissues contain both PKCγ and PKCε which have been implicated in protective roles against stroke and neural ischemia [61]. During and after middle cerebral artery occlusion, PKCγ migrates to synaptic membranes where it possibly modulates neurotransmission and cell survival [62].…”

Section: Pkcγ and Pkcε In Neural Tissuesmentioning

confidence: 99%

“…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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“…It is the only PKC isozyme that has been associated with oncogenesis [35,36]. There are several excellent review articles describing the role of PKCε in cardioprotection [37][38][39]. Although this review is primarily targeted to the cancer research aficionados, we have provided a comprehensive review of how PKCε interacts with various signaling pathways to regulate life and death of a cell and should benefit researchers in other fields as well.…”

Section: Introductionmentioning

confidence: 99%

Protein kinase Cε makes the life and death decision

Basu

Sivaprasad

2007

Cellular Signalling

144

154

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Cancer is caused by dysregulation in cellular signaling systems that control cell proliferation, differentiation and cell death. Protein kinase C (PKC), a family of serine/threonine kinases, plays an important role in the growth factor signal transduction pathway. PKCε, however, is the only PKC isozyme that has been considered as an oncogene. It can contribute to malignancy by enhancing cell proliferation or by inhibiting cell death. This review focuses on how PKCε collaborates with other signaling pathways, such as Ras/Raf/ERK and Akt, to regulate cell survival and cell death. We have also discussed how PKCε mediates is antiapoptotic signal by altering the level or function of proand antiapoptotic Bcl-2 family members.

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Protein Kinase C Isozymes in Stroke

Cited by 65 publications

References 33 publications

Poststroke neuronal rescue and synaptogenesis mediated in vivo by protein kinase C in adult brains

Poststroke neuronal rescue and synaptogenesis mediated in vivo by protein kinase C in adult brains

Protein kinase C as a stress sensor

Protein kinase Cε makes the life and death decision

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