Compound K Inhibits Autophagy-Mediated Apoptosis Through Activation of the PI3K-Akt Signaling Pathway Thus Protecting Against Ischemia/Reperfusion Injury

Abstract

Background/Aims: A series of reports revealed that autophagy and apoptosis exerted detrimental effects on the pathology of cardiac ischemia/reperfusion (I/R) injury. Ginsenoside compound K (CK), a major intestinal metabolite underlying the pharmacological actions of orally administered ginseng, has a protective effect against myocardial I/R injury. However, the molecular mechanisms by which CK protects against I/R injury remain unclear. In this study, we hypothesized that the cardioprotective effects of CK against I/R injury are mediated by inhibiting autophagy/apoptosis-related signaling pathways in H9c2 cardiomyocyte cells. Methods: H9c2 cells were incubated with CK and exposed to I/R. Cell viability and damage was analyzed by MTT and lactate dehydrogenase assays. Reactive oxygen species (ROS) generation, mitochondrial damage, and cell apoptosis were analyzed by flow cytometry and TUNEL staining. The expression of autophagy, apoptosis, and related signaling proteins was analyzed by Western blotting and immunofluorescence staining. Results: CK pretreatment promoted cell viability and attenuated ROS accumulation and intracellular mitochondrial damage induced by I/R injury Moreover, CK reduced autophagy by regulating the formation of phagocytic precursors to autophagosomes and also inhibited apoptosis through a mitochondrial-mediated pathway. Additionally the cardioprotective effect of CK against I/R injury was mainly through the activation of the PI3K-Akt signaling pathway. Conclusions: CK pretreatment inhibits autophagy-mediated apoptosis induced by I/R injury through the activation of the PI3K-Akt signaling pathway, which reveals that CK may be one of the key bioactive ingredients of ginseng for the treatment of myocardial I/R injury.

A predicted risk score based on the expression of 16 autophagy‑related genes for multiple myeloma survival

“…For KEGG pathways, the 'PI3K-Akt signaling pathway' was identified. It has been documented that there was a close association between PI3K-Akt signaling and autophagy (53)(54)(55). In general, activation of the PI3K-Akt signaling pathway may induce autophagy in numerous types of cancer (53)(54)(55)(56)(57)(58).…”

CD5L‑induced activation of autophagy is associated with hepatoprotection in ischemic reperfusion injury via the CD36/ATG7 axis

“…As the induction of autophagy is associated with an antiapoptotic effect during I/R (15), the autophagic flux was examined in I/R hepatocytes by assessing the expression of LC3B-II, a marker for autophagy, by western blotting of total cell lysates. The present study also identified that ATG7 upregulation was also associated with protection against I/R liver injury.…”

“…The autophagy salvage pathway is an additional means of energy generation in cells and can be activated by various cellular stressors, including I/R (14). Autophagy is a process of degradation and recycling of large molecules and dysfunctional organelles, protecting cells from apoptosis (15). As an inducer of autophagy, CD5L may serve a functional role in cytoprotection processes in macrophages and hepatocytes (12,16).…”

Gastrodin protects H9c2 cardiomyocytes against oxidative injury by ameliorating imbalanced mitochondrial dynamics and mitochondrial dysfunction

“…After culturing for 24 h and reaching ~70%–80% confluence, the cells were pretreated with the indicated concentrations of GAS (dissolved in culture medium) for 4 h before induction of ischemia-like injury or IR-like injury, or treatment with H 2 O 2 at the indicated concentrations. Ischemia-like or IR-like injury was induced in H9c2 cells using methods similar to those in a previous report [ 20 ]. For ischemia-like injury, the cells were deprived of oxygen, glucose, and serum for 9 h; briefly, the culture medium was replaced with serum- and glucose-free medium, and the plates were placed in an incubator with 1% O 2 , 94% N 2 , and 5% CO 2 air for 9 h. For IR-like injury, the cells were deprived of oxygen, glucose, and serum for 9 h, and then cultured under normal conditions in complete medium for an additional 3 h. For H 2 O 2 treatment, the cells were treated with the indicated concentrations of H 2 O 2 for different time periods.…”