Resveratrol attenuates hypoxia/reoxygenation-induced Ca2+ overload by inhibiting the Wnt5a/Frizzled-2 pathway in rat H9c2 cells

Wu, Xiang; Zhou, Shanshan; Zhu, Ning; Wang, Xianbao; Wen, Jing; Song, Xudong; Chen, Aihua

doi:10.3892/mmr.2014.2488

Cited by 18 publications

(9 citation statements)

References 37 publications

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“…We found that RSV treatment of the SH-SY5Y neuronal cells subjected to CoCl 2 -induced HYPX modulated the structural membrane depolarization integrity and enhanced biogenesis of mitochondria and restored mitochondrial and cytosolic ROS generation functions via modulation of TRPM2. We examined whether TRPM2 channel blockers (ACA and 2-APB) mediates the effects of HYPX and RSV on mitochondria, since results of recent studies have shown that ROS generation and Ca 2+ influx via VGCC activation is important for the mitochondrial response to stress and may be linked to neuronal apoptosis and death caused by HYPX 5,8 . Consistent with present findings, the mitochondria membrane depolarization, ROS generation, apoptosis and cell via stimulation of [Ca 2+ ] i increase and TRPM2 channel activation were upregulated in the SH-SY5Y cells but not in the HEK293 cells exposed to HYPX; importantly, these were totally reversed by RSV and TRPM2 channel blocker (ACA and 2-APB) treatments.…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

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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“…This study also has a few limitations. Firstly, besides the canonical Wnt/ β -catenin pathway, RSV may also regulate noncanonical Wnt pathway, such as Wnt5a [ 31 ]. Till now, at least 19 Wnt proteins were identified, forming a complex regulative network [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Resveratrol Enhances Cardiomyocyte Differentiation of Human Induced Pluripotent Stem Cells through Inhibiting Canonical WNT Signal Pathway and Enhancing Serum Response Factor‐miR‐1 Axis

Liu

Zhang

Zhao

et al. 2015

Stem Cells International

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Resveratrol (trans-3,5,4′-trihydroxystilbene) (RSV) is a natural polyphenol with protective effects over cardiac tissues and can affect cell survival and differentiation in cardiac stem cells transplantation. However, whether this agent can affect cardiomyocytes (CMs) differentiation of induced pluripotent stem cells (iPSCs) is not yet clear. This study explored whether RSV can affect CMs differentiation of human iPSCs. Under embryoid bodies (EBs) condition, the effect of RSV on the change of pluripotent markers, endoderm markers, mesoderm markers, and ectoderm markers was measured using qRT-PCR. Under CM differentiation culture, the effect of RSV on CM specific markers was also measured. The regulative role of RSV over canonical Wnt signal pathway and serum response factor- (SRF-) miR-1 axis and the functions of these two axes were further studied. Results showed that RSV had no effect on the self-renewal of human iPSCs but could promote mesoderm differentiation. Under CM differentiation culture, RSV could promote CM differentiation of human iPSCs through suppressing canonical Wnt signal pathway and enhancing SRF-miR-1 axis.

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“…The Wnt5a/Ca 2+ pathway, which is a well‐known Ca 2+ ‐modulating pathway, is activated upon inflammation or ischemia/anoxia stimulation. The signaling pathway is responsible for the intracellular Ca 2+ release . Upon binding to Wnt5a, the Frizzled‐2 receptor induces Ca 2+ release from intracellular stores and activates two kinases, Ca 2+ /CaMKII and PKC, in a G‐protein dependent manner .…”

Section: Discussionmentioning

confidence: 99%

Tao‐Hong‐Si‐Wu decoction reduces ischemia reperfusion rat myoblast cells calcium overloading and inflammation through the Wnt/IP3R/CAMKII pathway

Zhu

Linhua

et al. 2019

J of Cellular Biochemistry

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Limb ischemia reperfusion (LIRI) injury is associated with serious local and systemic effects. Reperfusion may augment tissue injury in excess of that produced by ischemia alone. Calcium overloading and inflammation are considered to be two of the pathological mechanisms of limb ischemia/ reperfusion (I/R) injury. Tao-Hong-Si-Wu decoction (THSWD) is a traditional Chinese herbal medicine with a powerful anti-inflammatory properties. We studied the probable restorative effect of THSWD on limb I/R-induced calcium overloading and inflammation in myoblast obtained from gastrocnemius muscle tissues of Sprague-Dawley rats (Frizzled Z5,a wnt5a blocker; KN-93, a calmodulin-dependent protein kinase II (CamkII) blocker; XeC, a IP3R blocker as positive controls). The simulated ischemia and reperfusion(I/R) solutions were used to imitate LIRI environment. The results showed that after I/R treatment, the secretion of proinflammatory factors (TNF-α and IL-1β) andWnt5a/Ca 2+ signal molecules (wnt5a, camkII, and IP3R) upregulated significantly, the Ca 2+ concentration enhanced too in myoblast cells. THSWD pretreatment decreased the secretion of TNF-α and IL-1β, Ca 2+ concentration; and abated the Wnt5a/Ca 2+ signal molecules of wnt5a, camkII and IP3R expression activated by I/R injury; but could not abated the Wnt11 and protein kinase C (PKC) expression significantly, the results was similar with Frizzled Z5 treatment cells. Our research illustrated that THSWD may have a mitigating effect on LIRI targeting Wnt/IP3R/CAMKII but not Wnt/IP3R/PKC signaling pathway for the first time. This study may encourage the use of THSWD in the critical clinical settings with LIRI.

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Resveratrol attenuates hypoxia/reoxygenation-induced Ca2+ overload by inhibiting the Wnt5a/Frizzled-2 pathway in rat H9c2 cells

Cited by 18 publications

References 37 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

Resveratrol Enhances Cardiomyocyte Differentiation of Human Induced Pluripotent Stem Cells through Inhibiting Canonical WNT Signal Pathway and Enhancing Serum Response Factor‐miR‐1 Axis

Tao‐Hong‐Si‐Wu decoction reduces ischemia reperfusion rat myoblast cells calcium overloading and inflammation through the Wnt/IP3R/CAMKII pathway

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