Targeting autophagy in cardiac ischemia/reperfusion injury: A novel therapeutic strategy

Aghaei, Mehrdad; Motallebnezhad, Morteza; Ghorghanlu, Sajjad; Jabbari, Ali; Enayati, Ahmad Ali; Rajaei, Maryam; Pourabouk, Mona; Moradi, Alireza; Alizadeh, Ali Mohammad; Khori, Vahid

doi:10.1002/jcp.28345

Cited by 77 publications

(53 citation statements)

References 121 publications

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“…Under short-term hypoxia and starvation conditions, autophagy is activated and plays a dual regulatory role. 48 Epicatechin gallate can protect HBMVECs from IR injury by ameliorating apoptosis and autophagy, but Alliin alleviates myocardial IR injury by promoting autophagy. 49,50 Initial autophagy is an important defence mechanism to remove damaged cell structures and aging organelles from degraded cells.…”

Section: Discussionmentioning

confidence: 99%

Bergenin Exerts Hepatoprotective Effects by Inhibiting the Release of Inflammatory Factors, Apoptosis and Autophagy via the PPAR-γ Pathway

Xiang

Chen

et al. 2020

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These authors contributed equally to this workObjective: Hepatic ischemia reperfusion (IR) limits the development of liver transplantation technology. The aim of this study was to explore the protective effects of Bergenin on hepatic IR, particularly the elimination of reactive oxygen species (ROS) and activation of the peroxisome proliferators activated receptor γ (PPAR-γ) pathway. Methods: Initial experiments were performed to confirm the non-toxicity of Bergenin. Mice were randomly divided into sham, IR, and IR + Bergenin (10, 20 and 40 mg/kg) groups, and serum and tissue samples were obtained at 2, 8 and 24 h for detection of liver enzymes (ALT and AST), inflammatory factors (TNF-α, IL-6 and IL-1β), ROS, cell death markers (Bcl-2, Bax, Beclin-1 and LC3) and related important pathways (PPAR-γ, P38 MAPK, NF-κB p65 and JAK2/STAT1). Results: Bergenin reduced the release of ROS, down-regulated inflammatory factors, and inhibited apoptosis and autophagy. Additionally, expression of PPAR-γ-related genes was increased and phosphorylation of P38 MAPK, NF-κB p65 and JAK2/STAT1-related proteins was decreased in Bergenin pre-treatment groups in a dose-dependent manner. Conclusion: Bergenin exerts hepatic protection by eliminating ROS, affecting the release of inflammatory factors, and influencing apoptosis-and autophagy-related genes via the PPAR-γ pathway in this model of hepatic IR injury.

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Section: Discussionmentioning

confidence: 99%

Bergenin Exerts Hepatoprotective Effects by Inhibiting the Release of Inflammatory Factors, Apoptosis and Autophagy via the PPAR-γ Pathway

Xiang

Chen

et al. 2020

DDDT

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“…21 In view of this, there has been a growing interest in developing novel protective stimuli applied at the onset of IR to limit subsequent injury. 22 Among these treatments, melatonin-a pleiotropic hormone produced mainly by the pineal gland-has gained much attention. 23 In a clinical trial, Fatemeh and colleagues showed that oral melatonin in renal transplant patients leaded to a significant reduction in complications related to IR injury and renal function markers such as BUN/ creatinine ratio.…”

Section: Discussionmentioning

confidence: 99%

Melatonin pretreatment alleviates renal ischemia‐reperfusion injury by promoting autophagic flux via TLR4/MyD88/MEK/ERK/mTORC1 signaling

et al. 2020

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Autophagy is an important mechanism for cellular homeostasis and survival during pathologic stress conditions in the kidney, such as ischemia‐reperfusion (IR) injury. In this study, renal IR was induced in female C57BL/6 mice after melatonin administration. Renal function, histological damage, inflammatory infiltration, cytokine production, oxidative stress, antioxidant capacity, autophagy changing, apoptosis levels, and autophagy‐associated intracellular signaling pathway were assessed to evaluate the impact of antecedent melatonin treatment on IR‐induced renal injury. The administration of melatonin resulted in significantly preserved renal function, and the protective effect was associated with ameliorated oxidative stress, limited pro‐inflammatory cytokine production, and neutrophil and macrophage infiltration. Moreover, autophagic flux was increased after melatonin administration while the apoptosis levels were decreased in the melatonin‐pretreated mice. Using TAK‐242 and CRX‐527, we confirmed that MyD88‐dependent TLR4 and MEK/ERK/mTORC1 signaling participated in melatonin‐induced autophagy in IR mice. Collectively, our results provide novel evidence that antecedent melatonin treatment provides protection for the kidney against IR injury by enhancing autophagy, as regulated by the TLR4/MyD88/MEK/ERK/mTORC1 signaling pathway. Therefore, melatonin preconditioning offers a potential therapeutic approach to prevent renal IR injury related to various clinical conditions.

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“…Myocardial ischemia/reperfusion (I/R) injury is a major contributing factor of morbidity and mortality in patients with ischemic heart disease or after cardiac surgery. 1,2 Studies identified various molecular and cellular mechanisms involved in the process of myocardial I/R. [3][4][5][6][7] Of these, intracellular calcium [Ca 2+ ]i overload is a critical one that leads to cardiomyocyte apoptosis and cell death.…”

Section: Introductionmentioning

confidence: 99%

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

Yuan¹,

Meng²,

Ma³

et al. 2019

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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.

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Targeting autophagy in cardiac ischemia/reperfusion injury: A novel therapeutic strategy

Cited by 77 publications

References 121 publications

<p>Bergenin Exerts Hepatoprotective Effects by Inhibiting the Release of Inflammatory Factors, Apoptosis and Autophagy via the PPAR-γ Pathway</p>

<p>Bergenin Exerts Hepatoprotective Effects by Inhibiting the Release of Inflammatory Factors, Apoptosis and Autophagy via the PPAR-γ Pathway</p>

Melatonin pretreatment alleviates renal ischemia‐reperfusion injury by promoting autophagic flux via TLR4/MyD88/MEK/ERK/mTORC1 signaling

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

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