The role of PI3K/AKT signaling pathway in myocardial ischemia-reperfusion injury

Deng, Ruiming; Zhou, Juan

doi:10.1016/j.intimp.2023.110714

Cited by 37 publications

(10 citation statements)

References 210 publications

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“…Among these compounds, irigenin and naringenin have an excellent a nity to AKT1 and autophagy-related proteins and are, therefore, considered important compounds for the treatment of MIRI by ZXGD. AKT1 has been shown to play a critical role in MIRI in previous studies [39]. AKT1 activation has a positive regulatory role in both mitochondrial damage and apoptosis during MIRI [40,41].…”

Section: Discussionmentioning

confidence: 83%

Zhishi xiebai guizhi decoction ameliorates mitochondrial dysfunction induced by myocardial ischemia-reperfusion injury in mice via the Autophagy-ACBP-TSPO axis

liu,

Cui,

Jiang

et al. 2024

Preprint

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Background Myocardial ischemia-reperfusion injury (MIRI) is often associated with oxidative stress, mitochondrial damage, programmed cell death, and autophagy. Protecting the mitochondrial function of myocardial tissue is critical for cardiac function. However, there is currently no effective treatment for MIRI. We aimed to determine whether zhishi xiebai guizhi decoction (ZXGD) attenuates MIRI through the autophagy-ACBP-TSPO axis. Methods A model of MIRI was established in mice by ligating the left anterior descending coronary artery for 30 min and reperfusion for 2 h. The myocardial injury was assessed by TTC-Evans blue and hematoxylin and eosin (HE) stains. The potential protein targets were identified using network analysis and molecular docking. Mitochondrial membrane potential and ATP production were detected using JC-1 assay and ATP assay kit, respectively. The target proteins were detected by western blotting, immunofluorescence analysis, and immunohistochemistry. Results ZXGD markedly attenuated myocardial damage, and enhanced cardiac function and mitochondrial morphology in mice accompanied with ischemia-reperfusion. It was found that AKT1-mTOR-mediated autophagy was possibly involved in the pretreatment of ZXGD on MIRI by network analysis and molecular docking. Experiments in vivo confirmed that ZXGD could inhibit myocardium autophagy, partly through activating the AKT1-mTOR signaling pathway. Furthermore, we revealed that ZXGD could promote ACBP expression and ACBP-TSPO binding in the myocardium, which might result from the regulation of autophagy. Conclusion ZXGD pretreatment significantly ameliorates MIRI by activating the autophagy-ACBP-TSPO axis in mice.

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Section: Discussionmentioning

confidence: 83%

Zhishi xiebai guizhi decoction ameliorates mitochondrial dysfunction induced by myocardial ischemia-reperfusion injury in mice via the Autophagy-ACBP-TSPO axis

liu,

Cui,

Jiang

et al. 2024

Preprint

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“…However, when an atheroma continues fatty substance buildup and forms a plaque, it may rupture. As already discussed, when this occurs, the plaque debris may eventually interrupt the blood flow to a portion of the heart, resulting in hypoxia and glucose deprivation in the blood-deprived cells; hypoxia is a major stimulus for free radical generation, which is highly destructive to cellular and molecular physiology, especially at the mitochondrial level [24,52]. Thus, neutralizing free radicals (ROS/RNS) in hypoxic tissue is highly effective in minimizing some of the ensuing molecular damage.…”

Section: Melatonin's Protective Actions Against Cvd and Cardiac Damagementioning

confidence: 99%

Mitochondrial Melatonin: Beneficial Effects in Protecting against Heart Failure

Reiter,

Sharma,

Chuffa

et al. 2024

Life

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Cardiovascular disease is the cause of physical infirmity and thousands of deaths annually. Typically, during heart failure, cardiomyocyte mitochondria falter in terms of energy production and metabolic processing. Additionally, inflammation and the accumulation of non-contractile fibrous tissue contribute to cardiac malfunction. Melatonin, an endogenously produced molecule, experimentally reduces the initiation and progression of atherosclerotic lesions, which are often the basis of coronary artery disease. The current review critically analyzes published data related to the experimental use of melatonin to forestall coronary artery pathologies. Collectively, these studies document melatonin’s anti-atherosclerotic actions in reducing LDL oxidation and triglyceride levels, lowering endothelial malfunction, limiting adhesion molecule formation, preventing macrophage polarization to the M1 pro-inflammatory phenotype, changing cellular metabolism, scavenging destructive reactive oxygen species, preventing the proliferation and invasion of arterial smooth muscle cells into the lesioned area, restricting the ingrowth of blood vessels from the vasa vasorum, and solidifying the plaque cap to reduce the chance of its rupture. Diabetic hyperglycemia, which aggravates atherosclerotic plaque formation, is also inhibited by melatonin supplementation in experimental animals. The potential value of non-toxic melatonin as a possible inhibitor of cardiac pathology in humans should be seriously considered by performing clinical trials using this multifunctional molecule.

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“…The pathway can reduce the degree of cell damage and promote cell survival by reducing the expression of inflammatory factors [84]. In addition, PI3K/Akt can activate nitric oxide synthase to push the production and removal of oxygen free radicals in the body into a dynamic equilibrium state [85].…”

Section: Pi3k/akt Signaling Pathwaymentioning

confidence: 99%

“…However, excessive activation of the PI3K/Akt signaling pathway may also have a negative impact on I/R injury. Excessive Akt activation may lead to mitochondrial dysfunction and calcium ion homeostasis imbalance, promote inflammatory response and cytokine release, and lead to increased tissue damage and cell death [85]. Therefore, balancing and regulating the activity of the PI3K/Akt signaling pathway is important for the treatment of I/R injury.…”

Section: Genital Systemmentioning

confidence: 99%

Exosomes-Mediated Signaling Pathway: A New Direction for Treatment of Organ Ischemia-Reperfusion Injury

Wang,

Xu,

Yan

et al. 2024

Biomedicines

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Ischemia reperfusion (I/R) is a common pathological process which occurs mostly in organs like the heart, brain, kidney, and lung. The injury caused by I/R gradually becomes one of the main causes of fatal diseases, which is an urgent clinical problem to be solved. Although great progress has been made in therapeutic methods, including surgical, drug, gene therapy, and transplant therapy for I/R injury, the development of effective methods to cure the injury remains a worldwide challenge. In recent years, exosomes have attracted much attention for their important roles in immune response, antigen presentation, cell migration, cell differentiation, and tumor invasion. Meanwhile, exosomes have been shown to have great potential in the treatment of I/R injury in organs. The study of the exosome-mediated signaling pathway can not only help to reveal the mechanism behind exosomes promoting reperfusion injury recovery, but also provide a theoretical basis for the clinical application of exosomes. Here, we review the research progress in utilizing various exosomes from different cell types to promote the healing of I/R injury, focusing on the classical signaling pathways such as PI3K/Akt, NF-κB, Nrf2, PTEN, Wnt, MAPK, toll-like receptor, and AMPK. The results suggest that exosomes regulate these signaling pathways to reduce oxidative stress, regulate immune responses, decrease the expression of inflammatory cytokines, and promote tissue repair, making exosomes a competitive emerging vector for treating I/R damage in organs.

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The role of PI3K/AKT signaling pathway in myocardial ischemia-reperfusion injury

Cited by 37 publications

References 210 publications

Zhishi xiebai guizhi decoction ameliorates mitochondrial dysfunction induced by myocardial ischemia-reperfusion injury in mice via the Autophagy-ACBP-TSPO axis

Zhishi xiebai guizhi decoction ameliorates mitochondrial dysfunction induced by myocardial ischemia-reperfusion injury in mice via the Autophagy-ACBP-TSPO axis

Mitochondrial Melatonin: Beneficial Effects in Protecting against Heart Failure

Exosomes-Mediated Signaling Pathway: A New Direction for Treatment of Organ Ischemia-Reperfusion Injury

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