Differential expression of TRPM2 and TRPV4 channels and their potential role in oxidative stress-induced cell death in organotypic hippocampal culture

Bai, Ji‐Zhong; Lipski, Janusz

doi:10.1016/j.neuro.2010.01.001

Cited by 104 publications

(93 citation statements)

References 69 publications

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“…4G), similar to previous observations in freshly isolated WT and gKO myocytes (26). Elevated mitochondrial O 2 .Ϫ in gKO-GFP myocytes (Fig. 4B) were substantially reduced by expression of Trpm2 (Fig.…”

Section: Methodssupporting

confidence: 90%

“…This is due to Ca 2ϩ entry via Trpm2 channels, thereby depolarizing plasma membrane and resulting in decreased NOX-mediated ROS production in WT phagocytes (13). Similarly, in pyramidal neurons subjected to oxidant injury, inhibition of Trpm2 results in enhanced cellular damage (2), confirming that Trpm2 reduces oxidative stress.…”

Section: Discussionmentioning

confidence: 89%

“…Loss of Trpm2 in cardiac myocytes resulted in mitochondrial dysfunction as indicated by lower ⌬ m , reduced mitochondrial Ca 2ϩ uptake due to both lower driving force and mitochondrial Ca 2ϩ uniporter (MCU) activity, impaired oxygen consumption resulting in lower ATP levels, and elevated cardiac ROS and mitochondrial O 2 .Ϫ levels when compared with WT myocytes (26). The second major finding is that mitochondrial dysfunction in gKO myocytes was rescued by Trpm2 but not by the loss-of-function E960D (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…In gKO myocytes expressing Trpm2 or its mutants, Trpm2 but not E960D reduced the elevated mitochondrial superoxide (O 2 .Ϫ ) levels in gKO myocytes. After hypoxia-reoxygenation (H/R), Trpm2 but not E906D or P1018L (inactivates Trpm2 current) lowered O 2 .Ϫ levels in gKO myocytes and only in the presence of extracellular Ca 2ϩ , indicating sustained Ca 2ϩ entry is necessary for Trpm2-mediated preservation of mitochondrial function. After ischemic-reperfusion (I/R), cardiac-specific Trpm2 KO hearts exhibited lower maximal first time derivative of LV pressure rise (ϩdP/dt) than WT hearts in vivo.…”

mentioning

confidence: 99%

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Ca²⁺entry via Trpm2 is essential for cardiac myocyte bioenergetics maintenance

Hoffman

Miller

Wang

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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Five days post-injection, gKO-GFP heart slices had higher reactive oxygen species (ROS) levels but lower oxygen consumption rate (OCR) than WT-GFP heart slices. Trpm2 but not E960D decreased ROS and restored OCR in gKO hearts back to normal levels. In gKO myocytes expressing Trpm2 or its mutants, Trpm2 but not E960D reduced the elevated mitochondrial superoxide (O 2 .Ϫ ) levels in gKO myocytes. After hypoxia-reoxygenation (H/R), Trpm2 but not E906D or P1018L (inactivates Trpm2 current) lowered O 2 .Ϫ levels in gKO myocytes and only in the presence of extracellular Ca 2ϩ , indicating sustained Ca 2ϩ entry is necessary for Trpm2-mediated preservation of mitochondrial function. After ischemic-reperfusion (I/R), cardiac-specific Trpm2 KO hearts exhibited lower maximal first time derivative of LV pressure rise (ϩdP/dt) than WT hearts in vivo. After doxorubicin treatment, Trpm2 KO mice had worse survival and lower ϩdP/dt. We conclude 1) cardiac Trpm2-mediated Ca 2ϩ influx is necessary to maintain mitochondrial function and protect against H/R injury; 2) Ca 2ϩ influx via cardiac Trpm2 confers protection against H/R and I/R injury by reducing mitochondrial oxidants; and 3) Trpm2 confers protection in doxorubicin cardiomyopathy. ischemic cardiomyopathy; doxorubicin cardiomyopathy; voltage-independent Ca 2ϩ channels; cardiac Trpm2 currents; mitochondrial superoxide; hypoxia-reoxygenation IN MAMMALIAN CELLS, THE TRANSIENT receptor potential (Trp) protein superfamily is a diverse group of voltage-independent, cation-permeable channels organized into six subfamilies based on amino acid sequence homology (9, 30). Monomeric Trp proteins have six putative transmembrane (TM) domains and intracellular NH 2 and COOH termini. To form a functional channel, Trp proteins assemble into either homo-or heterotetramers, with the putative pore formed by loops between the fifth and sixth TM domains (21, 23). The Trp-melastatin (Trpm) subfamily consists of eight mammalian members (Trpm1-Trpm8)(30), of which Trpm2 (27), -m4, -m5, and -m6 (49) are expressed in the heart. Although Trpm4 is associated with conduction abnormalities and cardiac arrhythmias (1, 36), there is little information on the physiological and pathophysiological function of Trpm2 in the heart.

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Section: Methodssupporting

confidence: 90%

Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Ca²⁺entry via Trpm2 is essential for cardiac myocyte bioenergetics maintenance

Hoffman

Miller

Wang

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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“…TRPV4 is widely expressed in many cell types, such as, urothelial cells, airway epithelial cells, epidermal keratinocytes, smooth muscle cells, and chondrocytes (12), but its expression in brain is limited only to the hippocampus and circumventricular organs (2,17,18). In contrast to its weak expression in the brain, TRPV4 is well expressed in sensory neurons such as dorsal root and trigeminal ganglion neurons and autonomic neurons in the sympathetic ganglia (12).…”

mentioning

confidence: 99%

Axonal Neuropathy-associated TRPV4 Regulates Neurotrophic Factor-derived Axonal Growth

Jang

Jung

Kim

et al. 2012

Journal of Biological Chemistry

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Background:Because genetic linkage studies identified mutations in TRPV4 in patients with peripheral neuropathies, the function of TRPV4 in peripheral neurons is questioned. Results: TRPV4 was found to promote neurotrophic factor-driven neuritogenesis. Conclusion: TRPV4 mediates neurotrophic factor-driven neuritogenesis in peripheral neurons. Significance: This explains molecular mechanisms underlying neuritogenesis and maintenance of peripheral nerves.

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Tumor Metabolism‐Engineered Composite Nanoplatforms Potentiate Sonodynamic Therapy via Reshaping Tumor Microenvironment and Facilitating Electron–Hole Pairs’ Separation

Guan

Yin

et al. 2020

Adv Funct Materials

114

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Reactive oxygen species (ROS) depletion and low ROS production that result from the intratumoral redox metabolism equilibrium and low energy conversion efficiency from ultrasound mechanical energy to ROS‐represented chemical energy, respectively, are two vital inhibitory factors of sonodynamic therapy (SDT). To address the two concerns, a tumor metabolism‐engineered composite nanoplatform capable of intervening intratumoral ROS metabolism, breaking the redox equilibrium, and reshaping the tumor microenvironment is constructed to reinforce SDT against tumors. In this metabolism‐engineered nanoplatform, Nb2C nanosheets serve as the scaffold to accommodate TiO2 sonosensitizers and l‐buthionine‐sulfoximine. Systematic experiments show that such nanoplatforms can reduce ROS depletion via suppressing glutathione synthesis and simultaneously improving ROS production via the Nb2C‐enhanced production and separation of electron–hole pairs. Contributed by the combined effect, net ROS content can be significantly elevated, which results in the highly efficient anti‐tumor outcomes in vivo and in vitro. Moreover, the combined design principles, that is, tumor metabolism modulation for reducing ROS depletion and electron–hole pair separation for facilitating ROS production, can be extended to other ROS‐dependent therapeutic systems.

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Differential expression of TRPM2 and TRPV4 channels and their potential role in oxidative stress-induced cell death in organotypic hippocampal culture

Cited by 104 publications

References 69 publications

Ca²⁺entry via Trpm2 is essential for cardiac myocyte bioenergetics maintenance

Ca²⁺entry via Trpm2 is essential for cardiac myocyte bioenergetics maintenance

Axonal Neuropathy-associated TRPV4 Regulates Neurotrophic Factor-derived Axonal Growth

Tumor Metabolism‐Engineered Composite Nanoplatforms Potentiate Sonodynamic Therapy via Reshaping Tumor Microenvironment and Facilitating Electron–Hole Pairs’ Separation

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Differential expression of TRPM2 and TRPV4 channels and their potential role in oxidative stress-induced cell death in organotypic hippocampal culture

Cited by 104 publications

References 69 publications

Ca2+entry via Trpm2 is essential for cardiac myocyte bioenergetics maintenance

Ca2+entry via Trpm2 is essential for cardiac myocyte bioenergetics maintenance

Axonal Neuropathy-associated TRPV4 Regulates Neurotrophic Factor-derived Axonal Growth

Tumor Metabolism‐Engineered Composite Nanoplatforms Potentiate Sonodynamic Therapy via Reshaping Tumor Microenvironment and Facilitating Electron–Hole Pairs’ Separation

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Ca²⁺entry via Trpm2 is essential for cardiac myocyte bioenergetics maintenance

Ca²⁺entry via Trpm2 is essential for cardiac myocyte bioenergetics maintenance