Glutamate-mediated activation of protein kinase C in hippocampal neurons

Hasham, Mohammed Iqbal; Pelech, Steven; Krieger, Charles

doi:10.1016/s0304-3940(97)00382-0

Cited by 17 publications

(3 citation statements)

References 11 publications

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“…PKC downregulation has been shown to protect against glutamate neurotoxicity (Ahlemeyer et al, 2002; Favaron et al, 1990; Hasham et al, 1997), while calpain inhibition has been shown to abrogate neuronal cell death (Witt et al, 1994) and block Ca 2+ influx (Weiss et al, 1990). Similarly, PKC and calpain are thought to play a role in postmyocardial infarction ischemic cell death of multiple tissues (Bright et al, 2004; Padanilam, 2001; Piccoletti et al, 1992; Speechly-Dick et al, 1994), as inhibitors of these enzymes offer protective effects (Bevers et al, 2009, 2010; Koponen et al, 2003; Neuhof et al, 2008; Wagey et al, 2001; Wei et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

A Host GPCR Signaling Network Required for the Cytolysis of Infected Cells Facilitates Release of Apicomplexan Parasites

Millholland

Mishra

Dupont

et al. 2013

Cell Host & Microbe

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Summary Following intracellular replication, the apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii cause host cell cytolysis to facilitate parasite release and disease progression. Parasite exit from infected cells requires the interplay of parasite-derived proteins and host actin cytoskeletal changes; however, the host proteins underlying these changes remain obscure. We report the identification of a Gαq-coupled host-signaling cascade required for the egress of both P. falciparum and T. gondii. Gαq-coupled signaling results in protein kinase C (PKC)-mediated loss of the host cytoskeletal protein adducin and weakening of the cellular cytoskeleton. This cytoskeletal compromise induces catastrophic Ca2+ influx mediated by the mechanosensitive cation channel TRPC6, which activates host calpain that proteolyzes the host cytoskeleton allowing parasite release. Reinforcing the feasibility of targeting host proteins as an antiparasitic strategy, mammalian PKC inhibitors demonstrated activity in murine models of malaria and toxoplasmosis. Importantly, an orally bioavailable PKC inhibitor prolonged survival in an experimental cerebral malaria model.

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Section: Discussionmentioning

confidence: 99%

A Host GPCR Signaling Network Required for the Cytolysis of Infected Cells Facilitates Release of Apicomplexan Parasites

Millholland

Mishra

Dupont

et al. 2013

Cell Host & Microbe

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“…Several receptors such as glutamatergic receptors 37, cholinergic receptors 38, serotonergic receptors 39 and dopaminergic receptors 40 regulate the functions of PKC. PKC is a key regulator of neuronal signal transduction pathways that are crucial to learning and memory consolidation 41-45.…”

Section: Discussionmentioning

confidence: 99%

Reduced Activity of Protein Kinase C in the Frontal Cortex of Subjects with Regressive Autism: Relationship with Developmental Abnormalities

Chauhan²,

Chauhan³

2012

Int. J. Biol. Sci.

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Autism is a neurodevelopmental disorder with unknown etiology. In some cases, typically developing children regress into clinical symptoms of autism, a condition known as regressive autism. Protein kinases are essential for G-protein-coupled receptor-mediated signal transduction, and are involved in neuronal functions, gene expression, memory, and cell differentiation. Recently, we reported decreased activity of protein kinase A (PKA) in the frontal cortex of subjects with regressive autism. In the present study, we analyzed the activity of protein kinase C (PKC) in the cerebellum and different regions of cerebral cortex from subjects with regressive autism, autistic subjects without clinical history of regression, and age-matched control subjects. In the frontal cortex of subjects with regressive autism, PKC activity was significantly decreased by 57.1% as compared to age-matched control subjects (p = 0.0085), and by 65.8% as compared to non-regressed autistic subjects (p = 0.0048). PKC activity was unaffected in the temporal, parietal and occipital cortices, and in the cerebellum in both autism groups, i.e., regressive and non-regressed autism as compared to control subjects. These results suggest brain region-specific alteration of PKC activity in the frontal cortex of subjects with regressive autism. Further studies showed a negative correlation between PKC activity and restrictive, repetitive and stereotyped pattern of behavior (r= -0.084, p = 0.0363) in autistic individuals, suggesting involvement of PKC in behavioral abnormalities in autism. These findings suggest that regression in autism may be attributed, in part, to alterations in G-protein-coupled receptor-mediated signal transduction involving PKA and PKC in the frontal cortex.

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“…Memory in its basic form is dependent on synaptic remodeling, formation of dendritic spines, and mitochondria functionality [99, 100]. Isoforms of PKC are involved in multiple synaptic transmissions, including those involving glutamate, dopamine, acetylcholine, and serotonin [101–104]. The synaptic connections are intimately linked to cognitive processing and learning with different PKC isoforms being involved in distinct memory domains.…”

Section: Pkc and Admentioning

confidence: 99%

Common Mechanisms of Alzheimer's Disease and Ischemic Stroke: The Role of Protein Kinase C in the Progression of Age-Related Neurodegeneration

Lucke‐Wold

Turner

Logsdon

et al. 2014

JAD

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Ischemic stroke and Alzheimer’s disease (AD), despite being distinct disease entities, share numerous pathophysiological mechanisms such as those mediated by inflammation, immune exhaustion, and neurovascular unit compromise. An important shared mechanistic link is acute and chronic changes in protein kinase C (PKC) activity. PKC isoforms have widespread functions important for memory, blood-brain barrier maintenance, and injury repair that change as the body ages. Disease states accelerate PKC functional modifications. Mutated forms of PKC can contribute to neurodegeneration and cognitive decline. In some cases the PKC isoforms are still functional but are not successfully translocated to appropriate locations within the cell. The deficits in proper PKC translocation worsen stroke outcome and amyloid-β toxicity. Cross talk between the innate immune system and PKC pathways contribute to the vascular status within the aging brain. Unfortunately, comorbidities such as diabetes, obesity, and hypertension disrupt normal communication between the two systems. The focus of this review is to highlight what is known about PKC function, how isoforms of PKC change with age, and what additional alterations are consequences of stroke and AD. The goal is to highlight future therapeutic targets that can be applied to both the treatment and prevention of neurologic disease. Although the pathology of ischemic stroke and AD are different, the similarity in PKC responses warrants further investigation, especially as PKC-dependent events may serve as an important connection linking age-related brain injury.

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Glutamate-mediated activation of protein kinase C in hippocampal neurons

Cited by 17 publications

References 11 publications

A Host GPCR Signaling Network Required for the Cytolysis of Infected Cells Facilitates Release of Apicomplexan Parasites

A Host GPCR Signaling Network Required for the Cytolysis of Infected Cells Facilitates Release of Apicomplexan Parasites

Reduced Activity of Protein Kinase C in the Frontal Cortex of Subjects with Regressive Autism: Relationship with Developmental Abnormalities

Common Mechanisms of Alzheimer's Disease and Ischemic Stroke: The Role of Protein Kinase C in the Progression of Age-Related Neurodegeneration

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