Amyloid β‐peptide(1–42) and hydrogen peroxide‐induced toxicity are mediated by TRPM2 in rat primary striatal cultures

Fonfría, Elena; Marshall, Ian C. B.; Boyfield, Izzy; Skaper, Stephen D.; Hughes, Jane P.; Owen, Davina E.; Zhang, W; Miller, Barbara A.; Benham, Christopher D.; McNulty, Shaun

doi:10.1111/j.1471-4159.2005.03396.x

Cited by 186 publications

(165 citation statements)

References 28 publications

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“…Hypoxia induced Ca 2+ overload and death in rat neonatal cariomyocytes (44), pancreatic β-cells (45), rat brain striatal cells (46,47), monocytes (40), and endothelial cells (39). However, in fibroblasts, oxidative stress seems to cause an opposite response.…”

Section: Discussionmentioning

confidence: 99%

Hypoxic Stress Induces Transient Receptor Potential Melastatin 2 (TRPM2) Channel Expression in Adult Rat Cardiac Fibroblasts

2012

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Abstract. When cardiac tissue is exposed to hypoxia, myocytes are damaged, while fibroblasts are activated. However, it is unknown what changes are induced by hypoxia in cardiac fibroblasts. In this study, using the whole cell patch-clamp technique, we investigated the effect of hypoxia on membrane currents in fibroblasts primarily cultured from adult rat hearts. Cardiac fibroblasts were incubated for 24 h under normoxic or hypoxic conditions using Anaeropack. Hypoxia increased a current which reversed at around −20 mV in the cardiac fibroblasts. This current was inhibited by clotrimazole, which is an inhibitor of transient receptor potential melastatin 2 (TRPM2) channel and intermediate-conductance Ca 2+ -activated K + channel (KCa3.1). ADP ribose in the pipette solution enhanced this current. Quantitative RT-PCR revealed that mRNA of TRPM2, but not that of KCa3.1, was increased by hypoxia. RNA interference of TRPM2 prevented the development of the hypoxia-induced current. H 2 O 2 , an activator of TRPM2 channel, induced a higher [Ca 2+ ] i elevation in hypoxia-exposed cardiac fibroblasts than that in normoxia-exposed cells. We conclude that hypoxia induces TRPM2 channel expression in adult rat cardiac fibroblasts.

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Section: Discussionmentioning

confidence: 99%

Hypoxic Stress Induces Transient Receptor Potential Melastatin 2 (TRPM2) Channel Expression in Adult Rat Cardiac Fibroblasts

2012

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“…TRPM2 is permeable to calcium, potassium, and sodium and is activated by oxidant stress, ADP-ribose (ADPR), TNF-α, and intracellular calcium (20)(21)(22)(23). Each of these stimuli is increased during kidney ischemia (24,25).…”

Section: Introductionmentioning

confidence: 99%

TRPM2 mediates ischemic kidney injury and oxidant stress through RAC1

Gao¹,

Wang²,

Tadagavadi³

et al. 2014

J. Clin. Invest.

103

101

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Measurement of TBARs. The measurement of TBARS in the kidney was based on the formation of malondialdehyde (MDA) as described by Liu et al. (87).Statistics. All assays were performed in duplicate or triplicate. Data are reported as the means ± SEM. Statistical significance was assessed by an unpaired, 2-tailed Student's t test for single comparison or by ANOVA for multiple comparisons. P < 0.05 was considered statistically significant. GraphPad Prism (GraphPad Software) was used for statistical analyses and graphs.Study approval. All experiments involving mice were approved by the

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“…It is expressed in many cell types, including brain and hematopoietic cells (42). Extracellular signals that activate TRPM2 include oxidative stress, TNF␣, amyloid ␤-peptide, and concanavalin A (14,16,17,50,55). Stimulation with these extracellular signals is thought to result in production of intracellular ADP ribose, which activates TRPM2 by binding to the TRPM2 COOH-terminal NUDT9-H domain (16,20,27,39,40,50).…”

mentioning

confidence: 99%

“…Stimulation with these extracellular signals is thought to result in production of intracellular ADP ribose, which activates TRPM2 by binding to the TRPM2 COOH-terminal NUDT9-H domain (16,20,27,39,40,50). TRPM2 plays an important role in susceptibility to cell death induced by oxidative stress or TNF␣, dependent on an increase in the free intracellular calcium concentration ([Ca 2ϩ ] i ) (14,17,55). The protein tyrosine phosphatase-L1 (PTPL1) is a widely expressed, nonreceptor protein tyrosine phosphatase, which has an important role in cell survival and tumorigenesis (2,23,53).…”

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confidence: 99%

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Regulation of TRP channel TRPM2 by the tyrosine phosphatase PTPL1

Zhang¹,

Tong²,

Conrad³

et al. 2007

American Journal of Physiology-Cell Physiology

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, a member of the transient receptor potential (TRP) superfamily, is a Ca 2ϩ -permeable channel, which mediates susceptibility to cell death following activation by oxidative stress, TNF␣, or ␤-amyloid peptide. We determined that TRPM2 is rapidly tyrosine phosphorylated after stimulation with H 2O2 or TNF␣. Inhibition of tyrosine phosphorylation with the tyrosine kinase inhibitors genistein or PP2 significantly reduced the increase in [Ca 2ϩ ]i observed after H2O2 or TNF␣ treatment in TRPM2-expressing cells, suggesting that phosphorylation is important in TRPM2 activation. Utilizing a TransSignal PDZ domain array blot to identify proteins which interact with TRPM2, we identified PTPL1 as a potential binding protein. PTPL1 is a widely expressed tyrosine phosphatase, which has a role in cell survival and tumorigenesis. Immunoprecipitation and glutathione-Stransferase pull-down assays confirmed that TRPM2 and PTPL1 interact. To examine the ability of PTPL1 to modulate phosphorylation or activation of TRPM2, PTPL1 was coexpressed with TRPM2 in human embryonic kidney-293T cells. This resulted in significantly reduced TRPM2 tyrosine phosphorylation, and inhibited the rise in [Ca 2ϩ ]i and the loss of cell viability, which follow H2O2 or TNF␣ treatment. Consistent with these findings, reduction in endogenous PTPL1 expression with small interfering RNA resulted in increased TRPM2 tyrosine phosphorylation, a significantly greater rise in [Ca 2ϩ ]i following H2O2 treatment, and enhanced susceptibility to H 2O2-induced cell death. Endogenous TRPM2 and PTPL1 was associated in U937-ecoR cells, confirming the physiological relevance of this interaction. These data demonstrate that tyrosine phosphorylation of TRPM2 is important in its activation and function and that inhibition of TRPM2 tyrosine phosphorylation reduces Ca 2ϩ influx and protects cell viability. They also suggest that modulation of TRPM2 tyrosine phosphorylation is a mechanism through which PTPL1 may mediate resistance to cell death.

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Amyloid β‐peptide(1–42) and hydrogen peroxide‐induced toxicity are mediated by TRPM2 in rat primary striatal cultures

Cited by 186 publications

References 28 publications

Hypoxic Stress Induces Transient Receptor Potential Melastatin 2 (TRPM2) Channel Expression in Adult Rat Cardiac Fibroblasts

Hypoxic Stress Induces Transient Receptor Potential Melastatin 2 (TRPM2) Channel Expression in Adult Rat Cardiac Fibroblasts

TRPM2 mediates ischemic kidney injury and oxidant stress through RAC1

Regulation of TRP channel TRPM2 by the tyrosine phosphatase PTPL1

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