<p>Dexmedetomidine protects H9c2 cardiomyocytes against oxygen-glucose deprivation/reoxygenation-induced intracellular calcium overload and apoptosis through regulating FKBP12.6/RyR2 signaling</p>

Abstract

Purpose Intracellular calcium ([Ca 2+ ]i) overload is a major cause of cell injury during myocardial ischemia/reperfusion (I/R). Dexmedetomidine (DEX) has been shown to exert anti-inflammatory and organ protective effects. This study aimed to investigate whether pretreatment with DEX could protect H9c2 cardiomyocytes against oxygen-glucose deprivation/reoxygenation (OGD/R) injury through regulating the Ca 2+ signaling. Methods H9c2 cardiomyocytes were subjected to OGD for 12 h, followed by 3 h of reoxygenation. DEX was administered 1 h prior to OGD/R. Cell viability, lactate dehydrogenase (LDH) release, level of [Ca 2+ ]i, cell apoptosis, and the expression of 12.6-kd FK506-binding protein/ryanodine receptor 2 (FKBP12.6/RyR2) and caspase-3 were assessed. Results Cells exposed to OGD/R had decreased cell viability, increased LDH release, elevated [Ca 2+ ]i level and apoptosis rate, down-regulated expression of FKBP12.6, and up-regulated expression of phosphorylated-Ser2814-RyR2 and cleaved caspase-3. Pretreatment with DEX significantly blocked the above-mentioned changes, alleviating the OGD/R-induced injury in H9c2 cells. Moreover, knockdown of FKBP12.6 by small interfering RNA abolished the protective effects of DEX. Conclusion This study indicates that DEX pretreatment protects the cardiomyocytes against OGD/R-induced injury by inhibiting [Ca 2+ ]i overload and cell apoptosis via regulating the FKBP12.6/RyR2 signaling. DEX may be used for preventing cardiac I/R injury in the clinical settings.

<p>Dexmedetomidine Attenuates Cellular Injury and Apoptosis in H9c2 Cardiomyocytes by Regulating p-38MAPK and Endoplasmic Reticulum Stress</p>

“…In regard to the mechanism at the cellular level, several studies have confirmed the cardioprotective effect of DEX in I/R injury based on H/R models. 23,24,41 The consistent conclusions advanced from these studies share similar outcomes with our conclusions, although the H/R models used varied among the studies. The major outcomes evaluated were cell viability, the apoptosis rate and LDH release, and by evaluating the expression of miR-208b, 23 intracellular calcium overload 24 and TLR4, 41 no ERS was found to be involved.…”

“…Furthermore, researchers have focused on studying other non-cardiac cells, such as endothelial cells, under IRI or H/R conditions 16,17 and examining several crucial ERS chaperones, proteins and apoptosis indicators produced by organs other than the heart under IRI or H/R conditions, 6,[18][19][20][21][22] finding that DEX can effectively regulate the function of non-cardiac cells and interfere in the endoplasmic reticulum stress signalling pathway under certain circumstances. Few studies have explored the function of DEX in H9c2 cardiomyocytes under H/R conditions; 23,24 however, the exact regulatory effect of DEX on ERS remains unknown. In recent years, an increasing number of basic research studies have focused on the p38MAPK signalling pathway; p38MAPK belongs to the family of MAPK-activated protein kinases and participates in many cellular processes, such as cell proliferation, survival and apoptosis.…”

The transcription factor Foxd3 induces spinal cord ischemia-reperfusion injury by potentiating microRNA-214-dependent inhibition of Kcnk2

“…All of the above plasmids were supplied by Shanghai Gene-Pharma Co., Ltd. (Shanghai, China). The dosages used for mimic NC and miR-214 mimic were 50 nM 20,21 , and 20 nM was used for pcDNA3.1, pcDNA3.1-Kcnk2, sh-NC and sh-Foxd3 22 . After 24 h of transfection, the cells underwent hypoxia (2 h) and reoxygenation (22 h) and were the collected for subsequent experiments.…”

Inhibition of cathepsin S attenuates myocardial ischemia/reperfusion injury by suppressing inflammation and apoptosis

“…Recent studies showed that pharmacological inhibition of inflammation and apoptosis alleviated I/R-induced myocardial injury in rats or hypoxia/ reoxygenation-induced injury in cardiomyocytes (J. Chen et al, 2019;Peng et al, 2020;Yuan et al, 2019;J. J. Zhang, Peng, Zhang, Meng, & Ji, 2017).…”