TRPM2 channel: A novel target for alleviating ischaemia‐reperfusion, chronic cerebral hypo‐perfusion and neonatal hypoxic‐ischaemic brain damage

Mai, Chendi; Mankoo, Harneet; Wei, Linyu; An, Xinfang; Li, Chaokun; Li, Dongliang; Jiang, Lin‐Hua

doi:10.1111/jcmm.14679

Cited by 25 publications

(24 citation statements)

References 74 publications

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“…RSV treatment increased the levels of cell viability (MTT) and protected neuronal cell count. Consistent with these observations, several studies have found that antioxidants such as curcumin neuroprotective actions through inhibition of TRPM2 channel and caspase activations against apoptosis and neuronal cell death under hypoxic conditions 38,43 . In the results of a recent study, RSV was shown to improve oxygen glucose deprivation-induced ischemic stroke via modulation mitochondrial dysfunction in the SSY5Y cells 44 .…”

Section: Discussionsupporting

confidence: 65%

“…Regulation of mitochondrial Ca 2+ uptake could counteract HYPX-induced mitochondrial membrane depolarization suppression, stimulate recovery of mitochondrial homeostasis, reduce neuron oxidative injury and apoptosis, and enhance tissue repair and regeneration in the SH-SY5Y neuronal cells 36,37 . The maintenance of mitochondrial membrane structure and physiological function depends on efficient mitochondrial function, which is restricted under hypoxic conditions 38 . It was reported that RSV modulates mitochondrial biogenesis and attenuates mitochondrial dysfunction, apoptosis and cell death in the rotenone-induced oxidative stress SH-SY5Y cellular Parkinson disease model 39,40 .…”

Section: Discussionmentioning

confidence: 99%

“…Accumulating evidence indicates that the injuring effects of HYPX are exerted at least in part by excessive ROS and cytokine generation 16,19,38 . We observed increased ROS, IL-1β and TNF-α generations and MDA levels in the SH-SY5Y cells exposed to HYPX, which were diminished by RSV treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Zn 2+ as a component of some antioxidant enzymes contributes to reducing excessive ROS generation in several cells and neurons 38 . Free Zn 2+ has apoptosis and oxidant actions via accumulation in the mitochondria for neurons 27 .…”

Section: Discussionmentioning

confidence: 99%

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Resveratrol attenuates hypoxia-induced neuronal cell death, inflammation and mitochondrial oxidative stress by modulation of TRPM2 channel

Akyuva

Nazıroğlu

2020

Sci Rep

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Hypoxia (HYpX) induced-overload ca 2+ entry results in increase of mitochondrial oxidative stress, inflammation and apoptosis in several neurons. Ca 2+ permeable TRPM2 channel was gated by ADPribose (ADPR) and reactive oxygen species (ROS), although its activity was modulated in HYPX-exposed neurons by resveratrol (RSV). The aim of this study was to evaluate if a therapy of RSV can modulate the effect of HYPX in the TRPM2 expressing SH-SY5Y neuronal and HEK293 (no expression of TRPM2) cell lines. The SH-SY5Y and HEK293 cells were divided into four groups as control, RSV (50 μM and 24 hours), and HYPX and RSV + HYPX. For induction of HYPX in the cells, CoCl 2 (200 μM and 24 hours) incubation was used. HYPX-induced intracellular Ca 2+ responses to TRPM2 activation were increased in the SH-SY5Y cells but not in the HEK293 cells from coming H 2 o 2 and ADPR. RSV treatment improved intracellular ca 2+ responses, mitochondrial function, suppressed the generation of cytokine (IL-1β and tnf-α), cytosolic and mitochondrial ROS in the SH-SY5Y cells. Intracellular free Zn 2+ , apoptosis, cell death, PARP-1, TRPM2 expression, caspase −3 and −9 levels are increased through activating TRPM2 in the SH-SY5Y cells exposed to the HYPX. However, the values were decreased in the cells by RSV and TRPM2 blockers (ACA and 2-APB). In SH-SY5Y neuronal cells exposed to HYPX conditions, the neuroprotective effects of RSV were shown to be exerted via modulation of oxidative stress, inflammation, apoptosis and death through modulation of TRPM2 channel. RSV could be used as an effective agent in the treatment of neurodegeneration exposure to HYPX.Extensive death in neurons was induced by acute hypoxia, because disability and mortality of the neurons were increased by acute hypoxia 1 . Low blood flow to the tissue and low oxygen content of blood result in hypoxia and ischemic condition 2 . Cell survival decreased in the absence of oxygen, because ATP generation requires oxygen consumption in mitochondria 3 . Mitochondria is a main source of reactive oxygen species (ROS) generation 4 . Accumulating evidence indicates that the hypoxia and ischemic conditions result in excessive ROS generation, inflammation and apoptosis through the increase of membrane depolarization in mitochondria of neurons 5,6 . The increase of mitochondrial membrane depolarization was induced by the increase of intracellular free Ca 2+ ([Ca 2+ ] i ) concentration. Recently, hypoxia-induced mitochondria ROS generation was inhibited through modulation of voltage gated calcium channel (VGCC) in the heart cells by resveratrol (RSV) treatment 7,8 . Hence, RSV can be useful for treatment of hypoxia in neuronal cells by modulation of mitochondrial ROS generation and the subject should be clarified in the hypoxia-induced SH-SY5Y neuronal cells.Several neuronal physiological functions such as mitochondria and cell development are triggered by the changes of the [Ca 2+ ] i concentration 4 . In addition, several neurotoxicity functions such as apoptosis and inflammation in hypoxia are...

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Section: Discussionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Resveratrol attenuates hypoxia-induced neuronal cell death, inflammation and mitochondrial oxidative stress by modulation of TRPM2 channel

Akyuva

Nazıroğlu

2020

Sci Rep

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“…The TRPM2 channel is highly sensitive to ROS due to the potent capacity of ROS to promote ADPR generation (Jiang et al, 2010). Studies using transgenic TRPM2-knockout (TRPM2-KO) mice and/or derived cell cultures provide compelling evidence to show the TRPM2 channel expression in neurons, microglia, astrocytes, neuro-endothelial cells, and pericytes in the brain and demonstrate its crucial role in mediating brain damage induced by various pathological conditions (Li et al, 2015;Jiang et al, 2018;Malko et al, 2019;Mai et al, 2020). For example, a recent study introducing TRPM2-KO in the APP/PS1 mice has disclosed a key role of the TRPM2 channel in Aβ-induced synaptic deficits, microglial cell activation, and age-related impairment in learning and memory (Ostapchenko et al, 2015).…”

Section: Perspective On Roles Of Oxidative Stress and Trpm2 Channel Imentioning

confidence: 99%

Predisposition to Alzheimer’s and Age-Related Brain Pathologies by PM2.5 Exposure: Perspective on the Roles of Oxidative Stress and TRPM2 Channel

et al. 2020

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Accumulating epidemiological evidence supports that chronic exposure to ambient fine particular matters of <2.5 µm (PM2.5) predisposes both children and adults to Alzheimer's disease (AD) and age-related brain damage leading to dementia. There is also experimental evidence to show that PM2.5 exposure results in early onset of AD-related pathologies in transgenic AD mice and development of AD-related and age-related brain pathologies in healthy rodents. Studies have also documented that PM2.5 exposure causes AD-linked molecular and cellular alterations, such as mitochondrial dysfunction, synaptic deficits, impaired neurite growth, neuronal cell death, glial cell activation, neuroinflammation, and neurovascular dysfunction, in addition to elevated levels of amyloid β (Aβ) and tau phosphorylation. Oxidative stress and the oxidative stress-sensitive TRPM2 channel play important roles in mediating multiple molecular and cellular alterations that underpin AD-related cognitive dysfunction. Documented evidence suggests critical engagement of oxidative stress and TRPM2 channel activation in various PM2.5-induced cellular effects. Here we discuss recent studies that favor causative relationships of PM2.5 exposure to increased AD prevalence and AD-and age-related pathologies, and raise the perspective on the roles of oxidative stress and the TRPM2 channel in mediating PM2.5-induced predisposition to AD and age-related brain damage.

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TRPM2 knockdown attenuates myocardial apoptosis and promotes autophagy in HFD/STZ-induced diabetic mice via regulating the MEK/ERK and mTORC1 signaling pathway

Hu,

Lin

2024

Mol Cell Biochem

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Diabetic cardiomyopathy (DCM) is a major complication of diabetes. Transient receptor potential melastatin 2 (TRPM2) activity increases in diabetic oxidative stress state, and it is involved in myocardial damage and repair. We explore the protective effect of TRPM2 knockdown on the progression of DCM. A type 2 diabetes animal model was established in C57BL/6N mice by long-term high-fat diet (HFD) feeding combined with a single injection of 100-mg/kg streptozotocin (STZ). Genetic knockdown of TRPM2 in heart was accomplished by the intravenous injection via the tail vein of adeno-associated virus type 9 carrying TRPM2 shRNA. Neonatal rat ventricular myocytes was exposed to 45 mM of high-glucose (HG) stimulation for 72 h in vitro to mimic the in vivo conditions. Western blot, real-time quantitative PCR (RT-qPCR), immunohistochemistry and fluorescence, electron, CCK-8, and flow cytometry were used to evaluate the phenotype of cardiac inflammation, fibrosis, apoptosis, and autophagy. Mice with HFD/STZ-induced diabetes exhibited systolic and diastolic dysfunction, as demonstrated by increased myocardial apoptosis and autophagy inhibition in the heart. Compared to control group, the protein expression of TRPM2, bax, cleaved caspase-3, and P62 was significantly elevated, and the protein expression of bcl-2 and LC3-II was significantly decreased in the myocardial tissues of the HFD/STZ-induced diabetes group. Knockdown of TRPM2 significantly reversed the HFD/STZ-induced myocardial apoptosis and autophagy inhibition. TRPM2 silencing attenuated HG-induced apoptosis and autophagy inhibition in primary cardiomyocytes via regulating the MEK/ERK mTORC1 signaling pathway. TRPM2 knockdown attenuates hyperglycemia-induced myocardial apoptosis and promotes autophagy in HFD/STZ-induced diabetic mice or HG-stimulated cardiomyocytes via regulating the MEK/ERK and mTORC1 signaling pathway.

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TRPM2 channel: A novel target for alleviating ischaemia‐reperfusion, chronic cerebral hypo‐perfusion and neonatal hypoxic‐ischaemic brain damage

Cited by 25 publications

References 74 publications

Resveratrol attenuates hypoxia-induced neuronal cell death, inflammation and mitochondrial oxidative stress by modulation of TRPM2 channel

Resveratrol attenuates hypoxia-induced neuronal cell death, inflammation and mitochondrial oxidative stress by modulation of TRPM2 channel

Predisposition to Alzheimer’s and Age-Related Brain Pathologies by PM2.5 Exposure: Perspective on the Roles of Oxidative Stress and TRPM2 Channel

TRPM2 knockdown attenuates myocardial apoptosis and promotes autophagy in HFD/STZ-induced diabetic mice via regulating the MEK/ERK and mTORC1 signaling pathway

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