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

Abstract

Background: Myocardial ischaemia-reperfusion injury (IRI) has been confirmed to induce endoplasmic reticulum stress (ERS) when myocardial cell function continues to deteriorate to a certain degree. The clinical applications of effective tested strategies are sometimes inconsistent with the applications evaluated in experiments, although reasonable mechanisms and diverse signalling pathways have been broadly explored. Dexmedetomidine (DEX) has been shown to attenuate IRI of the heart in animal studies. This study aimed to determine whether DEX can protect injured cardiomyocytes under hypoxia/reoxygenation (H/R) at the cellular level and whether the mechanism is related to ERS and the p38 MAPK pathway. Methods: H9c2 cells were subjected to H/R or thapsigargin (TG) to build a model. DEX or 4-PBA was added to the medium either 1 h or 24 h before modelling, respectively. Model parameters were determined by assessing cell viability and injury, which were measured by assessing cell counting kit-8 (CCK8), lactate dehydrogenase (LDH) release and flow cytometry results, and the expression of GRP78, CHOP and caspase-12. In addition, the protein expression of p38MAPK and p-p38MAPK was examined, and SB202190, a negative regulator, was also preincubated in medium. Results: Compared to that of cells in the control group, the activity of cells in the H/R and TG groups was decreased dramatically, and the LDH concentration and proportion of apoptotic cells were increased. DEX could correspondingly reverse the changes induced by H/R or TG. Additionally, DEX effectively attenuated ERS defined as increased expression of GRP78, CHOP and caspase-12. Additionally, DEX could obviously depress the P38 MAPK phosphorylation and high p-p38 MAPK expression in the TG group, indicating DEX has a function similar to that of SB202190. Conclusion: H/R injury in H9c2 cells can lead to abnormal ERS and apoptosis, as well as activation of the p38MAPK signalling pathway. DEX can protect cardiomyocytes by intervening in ERS, regulating p38MAPK and the downstream apoptotic signalling pathway.

Dexmedetomidine protects cardiomyocytes against hypoxia/reoxygenation injury via multiple mechanisms

“…Our results showed that Dex significantly improved the cell viability of H9c2 cells under H/R conditions. These results are in line with those of previous studies that also found that Dex protected H9c2 cells from H/R injury 14,15 …”

“…Our findings are following those of previous studies that suggest that Dex ameliorates oxidative stress in different cells. 14,20 However, little is known about the mechanisms underlying the antioxidative effects of Dex. We demonstrated that Dex treatment upregulated catalase and inhibited catalase, thereby partially inhibiting the protective effects of Dex.…”

Dexmedetomidine preconditioning alleviates H2O2-induced oxidative stress and apoptosis in human umbilical vein endothelial cells via p38MAPK signaling pathway

“…Western blot results showed that the expression of p-p38MAPK decreased signi cantly, while the expression of p-ERK1/2 increased signi cantly. In other studies, it has been found that Dex has a similar function to SB202190, which can alleviate hypoxia / reoxygenation injury of cardiomyocytes by inhibiting p38MAPK and downstream apoptosis signal pathway [42]. These results strongly suggest that Dex has the same effect as SB202190, and further con rm that Dex can protect HUVECs from oxidative stress by inhibiting p38MAPK pathway.…”

Dexmedetomidine Attenuates Ischemia/Reperfusion-Induced Myocardial Inflammation and Apoptosis Through Inhibiting Endoplasmic Reticulum Stress Signaling

“… 19 Dexmedetomidine also attenuated apoptosis and cell injury in cardiomyocytes subjected to hypoxia/reoxygenation or H 2 O 2 via regulating the ERS signaling. 32 , 33 However, these previous studies failed to detect the expression of key stress sensor protein PERK or its phosphorylation, compromising the evaluation of the effect of dexmedetomidine on ERS signaling. Moreover, these studies did not assess myocardial inflammation which is a major ERS-mediated outcome.…”