Involvement of TRP-like channels in the acute ischemic response of hippocampal CA1 neurons in brain slices

Lipski, Janusz; Park, Thomas I-H; Li, Dong; Lee, Stanley Chun-Wei; Trevarton, Alexander J.; Chung, Kenny Kwok Hin; Freestone, Peter S.; Bai, Ji‐Zhong

doi:10.1016/j.brainres.2006.01.016

Cited by 107 publications

(74 citation statements)

References 65 publications

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“…The activation of transient receptor potential melastatin (TRPM) channels, primarily the Ca 2+ -permeable TRPM2 (Lipski et al, 2006;Jia et al, 2011) and TRPM7 channels (Aarts et al, 2003;Sun et al, 2009), has been associated to oxidative stress, in addition to anoxic and ischemic cell death. Another key event during stroke is acidosis, caused by the decrease in the supply of oxygen to the brain, which leads to calcium influx, and failure of oxidative phosphorylation, with an increase in lactate production and the switch to glycolytic metabolism, with the final decrease in tissue pH (Xiong et al, 2004;Gu et al, 2010).…”

Section: Intracellular Calcium Overloadmentioning

confidence: 99%

Role of the ubiquitin–proteasome system in brain ischemia: Friend or foe?

Caldeira

Salazar

Curcio

et al. 2014

Progress in Neurobiology

114

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A B S T R A C TThe ubiquitin-proteasome system (UPS) is a catalytic machinery that targets numerous cellular proteins for degradation, thus being essential to control a wide range of basic cellular processes and cell survival. Degradation of intracellular proteins via the UPS is a tightly regulated process initiated by tagging a target protein with a specific ubiquitin chain. Neurons are particularly vulnerable to any change in protein composition, and therefore the UPS is a key regulator of neuronal physiology. Alterations in UPS activity may induce pathological responses, ultimately leading to neuronal cell death. Brain ischemia triggers a complex series of biochemical and molecular mechanisms, such as an inflammatory response, an exacerbated production of misfolded and oxidized proteins, due to oxidative stress, and the breakdown of cellular integrity mainly mediated by excitotoxic glutamatergic signaling. Brain ischemia also damages protein degradation pathways which, together with the overproduction of damaged proteins and consequent upregulation of ubiquitin-conjugated proteins, contribute to the accumulation of ubiquitincontaining proteinaceous deposits. Despite recent advances, the factors leading to deposition of such aggregates after cerebral ischemic injury remain poorly understood. This review discusses the current knowledge on the role of the UPS in brain function and the molecular mechanisms contributing to UPS dysfunction in brain ischemia with consequent accumulation of ubiquitin-containing proteins. Chemical inhibitors of the proteasome and small molecule inhibitors of deubiquitinating enzymes, which promote the degradation of proteins by the proteasome, were both shown to provide neuroprotection in brain ischemia, and this apparent contradiction is also discussed in this review. ß

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Section: Intracellular Calcium Overloadmentioning

confidence: 99%

Role of the ubiquitin–proteasome system in brain ischemia: Friend or foe?

Caldeira

Salazar

Curcio

et al. 2014

Progress in Neurobiology

114

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“…On the other hand, 500 μM ADPR activated TRPM2 currents in rat striatal neurons even when buffering intracellular Ca 2+ close to 0 using 500 μM EGTA [23]. Further studies on hippocampal CA1 neurons using Ca 2+ imaging in an in vivo oxygen-glucose deprivation model [24], and studies on primary rat pancreatic beta cells measuring heat-activated calcium signals [11] imply a role of TRPM2 in these systems but do not provide patch-clamp recordings for these two primary cell types.…”

Section: Introductionmentioning

confidence: 98%

Synergistic regulation of endogenous TRPM2 channels by adenine dinucleotides in primary human neutrophils

et al. 2008

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SummaryThe Ca 2+ -permeable TRPM2 channel is a dual function protein that is activated by intracellular ADPR through its enzymatic pyrophosphatase domain with Ca 2+ acting as a co-factor. Other TRPM2 regulators include cADPR, NAADP and H 2 O 2 , which synergize with ADPR to potentiate TRPM2 activation. Although TRPM2 has been thoroughly characterized in overexpression or cell-line systems, little is known about the features of TRPM2 in primary cells. We here characterize the regulation of TRPM2 activation in human neutrophils and report that ADPR activates TRPM2 with an effective half-maximal concentration (EC 50 ) of 1 μM. Potentiation by Ca 2+ is dose-dependent with an EC 50 of 300 nM. Both cADPR and NAADP activate TRPM2, albeit with lower efficacy than in the presence of subthreshold levels of ADPR (100 nM), which significantly shifts the EC 50 for cADPR from 44 μM to 3 μM and for NAADP from 95 μM to 1 μM. TRPM2 activation by ADPR can be suppressed by AMP with an IC 50 of 10 μM and cADPR-induced activation can be blocked by 8-Bromo-cADPR. We further show that 100 μM H 2 O 2 enables subthreshold concentrations of ADPR (100 nM) to activate TRPM2. We conclude that agonistic and antagonistic characteristics of TRPM2 as seen in overexpression systems are largely compatible with the functional properties of TRPM2 currents measured in human neutrophils, but the potencies of agonists in primary cells are significantly higher.

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“…Such effects were consistently shown with cocktail of blockers for glutamate NMDA and AMPA receptor and L-type calcium channels (MK-801, CNQX, and nimodipine), indicating the independent role of TRPM7 in mediating intracellular Ca 2+ elevation and subsequent cell death during the prolonged anoxia. In another study, the contribution of TRPM7 channels in cell membrane depolarization, intracellular Ca 2+ accumulation and cell swelling during the initial period of brain ischemia is also observed in native CA1 neurons of brain slices [78] . TRPM7 in vivo studies have been scarce for a period of time because both the knockout model and selective pharmacological agents are not available.…”

Section: Pathophysiological Relevance In Cerebral Ischemia and Strokementioning

confidence: 85%

TRPM7 in cerebral ischemia and potential target for drug development in stroke

Bae

Sun

2011

Acta Pharmacol Sin

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Searching for effective pharmacological agents for stroke treatment has largely been unsuccessful. Despite initial excitement, antagonists for glutamate receptors, the most studied receptor channels in ischemic stroke, have shown insuffi cient neuroprotective effects in clinical trials. Outside the traditional glutamate-mediated excitotoxicity, recent evidence suggests few non-glutamate mechanisms, which may also cause ionic imbalance and cell death in cerebral ischemia. Transient receptor potential melastatin 7 (TRPM7) is a Ca 2+ permeable, non-selective cation channel that has recently gained attention as a potential cation infl ux pathway involved in ischemic events. Compelling new evidence from an in vivo study demonstrated that suppression of TRPM7 channels in adult rat brain in vivo using virally mediated gene silencing approach reduced delayed neuronal cell death and preserved neuronal functions in global cerebral ischemia. In this review, we will discuss the current understanding of the role of TRPM7 channels in physiology and pathophysiology as well as its therapeutic potential in stroke.

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Involvement of TRP-like channels in the acute ischemic response of hippocampal CA1 neurons in brain slices

Cited by 107 publications

References 65 publications

Role of the ubiquitin–proteasome system in brain ischemia: Friend or foe?

Role of the ubiquitin–proteasome system in brain ischemia: Friend or foe?

Synergistic regulation of endogenous TRPM2 channels by adenine dinucleotides in primary human neutrophils

TRPM7 in cerebral ischemia and potential target for drug development in stroke

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