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

Yu, Yang; Wang, Hui; Song, Nan; Jiang, Youen; Zhang, Jun; Meng, Xiao Wen; Feng, Xiao; Liu, Hong; Peng, Ke; Ji, Fu

doi:10.2147/jir.s292263

Cited by 33 publications

(22 citation statements)

References 38 publications

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“…As shown in the present study, DEX alleviated neuroinflammation in mouse TBI models. Additionally, DEX directly regulates several cell death models (22,25,(48)(49)(50)(51). According to Gao et al (49), DEX induces the expression of the neuroglobin protein in hippocampal tissues and then inhibits neuronal apoptosis through the mitochondrial pathway.…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine alleviates early brain injury following traumatic brain injury by inhibiting autophagy and neuroinflammation through the ROS/Nrf2 signaling pathway

Feng

Zhu

et al. 2021

Mol Med Rep

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Traumatic brain injury (TBI) is a major public health problem and a major cause of mortality and disability that imposes a substantial economic burden worldwide. Dexmedetomidine (DEX), a highly selective α-2-adrenergic receptor agonist that functions as a sedative and analgesic with minimal respiratory depression, has been reported to alleviate early brain injury (EBI) following traumatic brain injury by reducing reactive oxygen species (ROS) production, apoptosis and autophagy. Autophagy is a programmed cell death mechanism that serves a vital role in neuronal cell death following TBI. However, the precise role of autophagy in DEX-mediated neuroprotection following TBI has not been confirmed. The present study aimed to investigate the neuroprotective effects and potential molecular mechanisms of DEX in TBI-induced EBI by regulating neural autophagy in a C57BL/6 mouse model. Mortality, the neurological score, brain water content, neuroinflammatory cytokine levels, ROS production, malondialdehyde levels and neuronal death were evaluated by TUNEL staining, Evans blue extravasation, ELISA, analysis of ROS/lipid peroxidation and western blotting. The results showed that DEX treatment markedly increased the survival rate and neurological score, increased neuron survival, decreased the expression of the LC3, Beclin-1 and NF-κB proteins, as well as the cytokines IL-1β, IL-6 and TNF-α, which indicated that DEX-mediated inhibition of autophagy and neuroinflammation ameliorated neuronal death following TBI. The neuroprotective capacity of DEX is partly dependent on the ROS/nuclear factor erythroid 2-related factor 2 signaling pathway. Taken together, the results of the present study indicated that DEX improves neurological outcomes in mice and reduces neuronal death by protecting against neural autophagy and neuroinflammation.

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Section: Discussionmentioning

confidence: 99%

Dexmedetomidine alleviates early brain injury following traumatic brain injury by inhibiting autophagy and neuroinflammation through the ROS/Nrf2 signaling pathway

Feng

Zhu

et al. 2021

Mol Med Rep

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“…Cells were incubated at 37 °C in an atmosphere of 5% CO 2 , and grown to 80% confluence before use. For oxygen glucose deprivation/ reoxygenation (OGD/R) treatment is the same as the description of our previous research (Yang et al, 2021b). Briefly, HEK293T were cultured in an anaerobic chamber containing 95% N 2 and 5% CO 2 for 6 h and then reoxygenated for 6 h to induce OGD/R condition.…”

Section: Establishment Of Renal Ischemia-reperfusion Model Cell Cultu...mentioning

confidence: 99%

Dexmedetomidine Attenuates Ferroptosis-Mediated Renal Ischemia/Reperfusion Injury and Inflammation by Inhibiting ACSL4 via α2-AR

et al. 2022

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Ischemia-reperfusion (I/R) injury is a serious clinical pathology associated with acute kidney injury (AKI). Ferroptosis is non-apoptotic cell death that is known to contribute to renal I/R injury. Dexmedetomidine (Dex) has been shown to exert anti-inflammatory and organ protective effects. This study aimed to investigate the detailed molecular mechanism of Dex protects kidneys against I/R injury through inhibiting ferroptosis. We established the I/R-induced renal injury model in mice, and OGD/R induced HEK293T cells damage in vitro. RNA-seq analysis was performed for identifying the potential therapeutic targets. RNA-seq analysis for differentially expressed genes (DEGs) reported Acyl-CoA synthetase long-chain family member 4 (ACSL4) related to ferroptosis and inflammation in I/R mice renal, which was validated in rodent renal. Liproxstatin-1, the specific small-molecule inhibitor of ferroptosis, significantly attenuated ferroptosis-mediated renal I/R injury with decreased LPO, MDA, and LDH levels, and increased GSH level. Inhibiting the activity of ACSL4 by the Rosiglitazone (ROSI) resulted in the decreased ferroptosis and inflammation, as well as reduced renal tissue damage, with decreasing LPO, MDA and LDH level, increasing GSH level, reducing COX2 and increasing GPx4 protein expression, and suppressing the TNF-α mRNA and IL-6 mRNA levels. Dex as a α2-adrenergic receptor (α2-AR) agonist performed renal protective effects against I/R-induced injury. Our results also revealed that Dex administration mitigated tissue damage, inhibited ferroptosis, and downregulated inflammation response following renal I/R injury, which were associated with the suppression of ACSL4. In addition, ACSL4 overexpression abolishes Dex-mediated protective effects on OGD/R induced ferroptosis and inflammation in HEK293T cells, and promotion of ACSL4 expression by α2-AR inhibitor significantly reversed the effects on the protective role of Dex. This present study indicated that the Dex attenuates ferroptosis-mediated renal I/R injury and inflammation by inhibiting ACSL4 via α2-AR.

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“…The signaling mechanism in which autophagy induces its effects on the endoplasmic reticulum remains an area for future research. However, a more recent study showed that the use of a highly selective agonist of α2-adrenergic receptors, dexmedetomidine improves myocardiocyte ischemic/reperfusion injury by down-regulation of the endoplasmic reticulum stress signaling pathway that includes glucose-regulated protein 78 (GRP78), protein kinase R-like endoplasmic reticulum kinase (PERK), homologous protein C/EBP (CHOP), inositol-requiring protein 1 (IRE1), and activating transcription factor 6 (ATF6) [50].…”

Section: Autophagy Of the Endoplasmic Reticulum Of Myocardiocytesmentioning

confidence: 99%

Myocardiocyte autophagy in the context of myocardiocytes regeneration: a potential novel therapeutic strategy

Marzoog

Власова

2022

Egypt J Med Hum Genet

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Background The regeneration strategy involves several aspects, such as reprogramming aspects, targeting pathophysiological processes, and inducing the physiological one. Autophagy targeting is a potential physiological/pathogenetic strategy to enhance myocardiocytes' function. Myocardiocytes' injury-related death remains to be the highest in our era. Unfortunately, myocardiocytes have a limited proliferation capacity to compensate for what was lost by infarction. However, partially injured myocardiocytes can be preserved by improving the autophagy process of myocardiocytes. Main text Autophagy induction involved controlling the cellular and subcellular environment as well as gene expression. Autophagy is well known to prolong the longevity of cell and human life. Inhibition of the mTOR receptor, proapoptotic gene Bnip3, IP3, and lysosome inhibitors, inhibition of microRNA-22 and overexpression of microRNA-99a, modulators of activated protein kinase with adenosine monophosphate, resveratrol, sirtuin activators, Longevinex and calcium lowering agents can promote physiological myocardiocyte autophagy and improve post-myocardial modulation and recovery speed. The paper aimed to assess autophagy role in myocardiocytes regeneration modulation. Conclusions The autophagy strategy can be applied to infarcted myocardiocytes, as well as heart failure. However, cell self-eating is not the preferred therapy for preserving injured myocardiocytes or causing regeneration.

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

Cited by 33 publications

References 38 publications

Dexmedetomidine alleviates early brain injury following traumatic brain injury by inhibiting autophagy and neuroinflammation through the ROS/Nrf2 signaling pathway

Dexmedetomidine alleviates early brain injury following traumatic brain injury by inhibiting autophagy and neuroinflammation through the ROS/Nrf2 signaling pathway

Dexmedetomidine Attenuates Ferroptosis-Mediated Renal Ischemia/Reperfusion Injury and Inflammation by Inhibiting ACSL4 via α2-AR

Myocardiocyte autophagy in the context of myocardiocytes regeneration: a potential novel therapeutic strategy

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