TRPC channels promote cerebellar granule neuron survival

Jia, Yichang; Zhou, Jian; Tai, Yilin; Wang, Yizheng

doi:10.1038/nn1870

Cited by 217 publications

(234 citation statements)

References 49 publications

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“…It is also worth noting that oxidative stress has been shown to activate TRPC3 and TRPC4 in endothelial cells (23) and that another submember of TRP channels, TRPM, has been reported to contribute to oxidative stress-induced cell death (23). However, in contrast to these reports suggesting that TRPCs contribute to increased cell death, Jia et al (16) showed that TPRC3 and TRPC6 played a role in promoting neuronal survival in response to serum deprivation. Taken together with our results, these studies support the notion that TRPCs play a role in regulating cell survival; however, whether they contribute to cell death or survival may be both cell and stress specific.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of TRPC3 increases apoptosis but not necrosis in response to ischemia-reperfusion in adult mouse cardiomyocytes

Shan

Marchase²,

Chatham

2008

American Journal of Physiology-Cell Physiology

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Shan D, Marchase RB, Chatham JC. Overexpression of TRPC3 increases apoptosis but not necrosis in response to ischemia-reperfusion in adult mouse cardiomyocytes. Am J Physiol Cell Physiol 294: C833-C841, 2008. First published January 9, 2008 doi:10.1152/ajpcell.00313.2007.-An increase in cytosolic Ca 2ϩ via a capacitative calcium entry (CCE)-mediated pathway, attributed to members of the transient receptor potential (TRP) superfamily, TRPC1 and TRPC3, has been reported to play an important role in regulating cardiomyocyte hypertrophy. Increased cytosolic Ca 2ϩ also plays a critical role in mediating cell death in response to ischemiareperfusion (I/R). Therefore, we tested the hypothesis that overexpression of TRPC3 in cardiomyocytes will increase sensitivity to I/R injury. Adult cardiomyocytes isolated from wild-type (WT) mice and from mice overexpressing TRPC3 in the heart were subjected to 90 min of ischemia and 3 h of reperfusion. After I/R, viability was 51 Ϯ 1% in WT mice and 42 Ϯ 5% in transgenic mice (P Ͻ 0.05). Apoptosis assessed by annexin V was significantly increased in the TRPC3 group compared with WT (32 Ϯ 1% vs. 21 Ϯ 3%; P Ͻ 0.05); however, there was no significant difference in necrosis between groups. Treatment of TRPC3 cells with the CCE inhibitor SKF-96365 (0.5 M) significantly improved cellular viability (54 Ϯ 4%) and decreased apoptosis (15 Ϯ 4%); in contrast, the L-type Ca 2ϩ channel inhibitor verapamil (10 M) had no effect. Calpain-mediated cleavage of ␣-fodrin was increased approximately threefold in the transgenic group following I/R compared with WT (P Ͻ 0.05); this was significantly attenuated by SKF-96365. The calpain inhibitor PD-150606 (25 M) attenuated the increase in both ␣-fodrin cleavage and apoptosis in the TPRC3 group. Increased TRPC3 expression also increased sensitivity to Ca 2ϩ overload stress, but it did not affect the response to TNF-␣-induced apoptosis. These results suggest that CCE mediated via TRPC may play a role in cardiomyocyte apoptosis following I/R due, at least in part, to increased calpain activation.

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Section: Discussionmentioning

confidence: 99%

Overexpression of TRPC3 increases apoptosis but not necrosis in response to ischemia-reperfusion in adult mouse cardiomyocytes

Shan

Marchase²,

Chatham

2008

American Journal of Physiology-Cell Physiology

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“…Such phytochemicals can induce a mild adaptive stress response in cells. Examples include resveratrol, a chemical in red wine that may protect against cardiovascular disease, which induces a stress resistance response mediated by a protein called Sir-2 (Tissenbaum and Guarente, 2001;Howitz et al, 2003); sulforaphane and curcumin, which are present at high levels in broccoli and curry powder, respectively, and activate the Nrf-2-antioxidant response element pathway resulting in the expression of phase 2 detoxifying and antioxidant enzymes (Faulkner et al, 1998); and allicin, from garlic, which activates transient receptor potential receptors, resulting in calcium influx and downstream signaling cascades that upregulate neurotrophic factor expression (Macpherson et al, 2005;Jia et al, 2007). Therefore, from both evolutionary and mechanistic perspectives, at least some beneficial effects of phytochemicals in the human diet may be mediated by hormetic mechanisms.…”

Section: Diet and Neurohormesismentioning

confidence: 99%

Awareness of Hormesis Will Enhance Future Research in Basic and Applied Neuroscience

Mattson

2008

Critical Reviews in Toxicology

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Hormesis is defined operationally as responses of cells or organisms to an exogenous or intrinsic factor (chemical, temperature, psychological challenge, etc.) in which the factor induces stimulatory or beneficial effects at low doses and inhibitory or adverse effects at high doses. The compendium of articles by Calabrese entitled "Neuroscience and Hormesis" provides a broad range of examples of neurobiological processes and responses to environmental factors that exhibit biphasic dose responses, the signature of hormesis. Nerve cell networks are the "first responders" to environmental challenges-they perceive the challenge and orchestrate coordinated adaptive responses that typically involve autonomic, neuroendocrine, and behavioral changes. In addition to direct adaptive responses of neurons to environmental stressors, cells subjected to a stressor produce and release molecules such as growth factors, cytokines, and hormones that alert adjacent and even distant cells to impending danger. The discoveries that some molecules (e.g., carbon monoxide and nitric oxide) and elements (e.g., selenium and iron) that are toxic at high doses play fundamental roles in cellular signaling or metabolism suggest that during evolution, organisms (and their nervous systems) coopted environmental toxins and used them to their advantage. Neurons also respond adaptively to everyday stressors, including physical exercise, cognitive challenges, and dietary energy restriction, each of which activates pathways linked to the production of neurotrophic factors and cellular stress resistance proteins. The development of interventions that activate hormetic signaling pathways in neurons is a promising new approach for the preventation and treatment of a range of neurological disorders. COMMENTARY ON NEUROSCIENCE AND HORMESISThe biphasic nature of responses to neurotransmitters, neurotrophic factors, cytokines, drugs of abuse, and treatments for a range of neurological disorders is underappreciated and often ignored in basic and applied neuroscience research. Calabrese demonstrates a broad understanding of basic principles of neuroscience, to which he applies his expertise in toxicology and hormesis to catalog hundreds of examples of "toxins," pharmacological agents, intrinsic signaling molecules, and behavioral factors that exhibit biphasic dose responses. The focus throughout the series of articles in "Neuroscience and Hormesis" is on the results of cell culture and in vivo experiments in which the effects of increasing doses of exogenous agents (toxins, neurotransmitters, peptide, hormones, drugs of abuse, etc.) on neuronal survival or plasticity or on animal behavior has been investigated. Calabrese aptly explores the existence of hormesis in most of the major areas of the field of neuroscience, ranging from developmental mechanisms (cell survival and neurite outgrowth) to synaptic plasticity to behavior to

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“…To determine whether PLC␥, PI(3)K, and protein tyrosine kinase were involved in activation of TRPC5 channels leading to neurite outgrowth, pharmacological blockers for tyrosine kinase (genistein), PLC (U73122), and PI(3)K (wortmannin, LY294002) were used. These widely used inhibitors were reported to show specificity for the indicated reactions (Akiyama et al, 1987;Bleasdale et al, 1990;Powis et al, 1994;Vlahos et al, 1994;Laurino et al, 2005;Li et al, 2005;Jia et al, 2007). In some cases, ATP, known to activate TRPC5 channels via PLC through stimulation of G-protein-controlled signaling (Shimizu et al, 2006), was also applied subsequent to CtxB.…”

Section: Activation Of Integrin Signaling Cascade By Ctxbmentioning

confidence: 99%

Induction of Calcium Influx through TRPC5 Channels by Cross-Linking of GM1 Ganglioside Associated with α5β1 Integrin Initiates Neurite Outgrowth

Wu¹,

Lu²,

Obukhov³

et al. 2007

J. Neurosci.

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Previous studies demonstrated that cross-linking of GM1 ganglioside with multivalent ligands, such as B subunit of cholera toxin (CtxB), induced Ca 2ϩ influx through an unidentified, voltage-independent channel in several cell types. Application of CtxB to undifferentiated NG108-15 cells resulted in outgrowth of axon-like neurites in a Ca 2ϩ influx-dependent manner. In this study, we demonstrate that CtxB-induced Ca 2ϩ influx is mediated by TRPC5 channels, naturally expressed in these cells and primary neurons. Both Ca 2ϩ influx and neurite induction were blocked by TRPC5 small interfering RNA (siRNA). Pretreatment of NG108-15 cells with neuraminidase increased cell-surface GM1 and greatly enhanced the signal. GM1 was not directly associated with TRPC5 but rather with ␣5␤1 integrin, which opened the channel through a signaling sequence after cross-linking of the GM1/integrin complex. This cascade included autophosphorylation of focal adhesion kinase and subsequent activation of phospholipase C␥ (PLC␥) and phosphoinositide-3 kinase [PI(3)K]. Pharmacological blockers that inhibited tyrosine kinase, PLC, and PI(3)K suppressed both CtxB-induced Ca 2ϩ influx and neurite outgrowth. These were also suppressed by SK&F96365, a nonspecific transient receptor potential channel blocker. Confocal immunocytochemistry revealed that GM1 cross-linking induced colocalization of GM1 with these signaling elements in sprouting regions of plasma membrane. In primary cerebellar granular neurons (CGNs), TRPC5 was detected at 2 d in vitro (2 DIV), a stage corresponding to CtxB-stimulated Ca 2ϩ influx. Neurite outgrowth in CGNs, determined at 3 DIV, was accelerated by CtxB and suppressed by TRPC5 siRNA and the above blockers. The crucial role of GM1 was indicated with CGNs from ganglio-series null mice, in which growth of axons was significantly retarded.

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TRPC channels promote cerebellar granule neuron survival

Cited by 217 publications

References 49 publications

Overexpression of TRPC3 increases apoptosis but not necrosis in response to ischemia-reperfusion in adult mouse cardiomyocytes

Overexpression of TRPC3 increases apoptosis but not necrosis in response to ischemia-reperfusion in adult mouse cardiomyocytes

Awareness of Hormesis Will Enhance Future Research in Basic and Applied Neuroscience

Induction of Calcium Influx through TRPC5 Channels by Cross-Linking of GM1 Ganglioside Associated with α5β1 Integrin Initiates Neurite Outgrowth

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