RESUMO
Aim To investigate the protective effect of resveratrol on oxidative stress injury of cardiomyocytes induced by high fat and its correlation with AMPK/mTC)RCl/p70S6K signaling pathway. Methods The model of cardiomyocyte lipotoxicity injury was established by palmitic acid (PA). Resveratrol pretreatment and MTT assay were used to detect cell proliferation. The expression of reactive oxygen species ( ROS) was detected by fluorescence and flow cytometry, and the levels of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) were detected by kit. The protein expression of AMPK/mTORCl/P70S6K signaling pathway and apoptosis related proteins were determined by Western blot. Results MIT results showed that the cell viability decreased significantly at 0. 4 mmol L-1 and 24 h-48 h stimulation time, re-spectively. Fluorescence and flow cytometry showed that the levels of ROS and MDA increased significantly and SOD activity decreased significantly when PA (0. 4 mmol • L"1) stimulated cells for 24 h compared with control group. Western blot showed that the expression of p-AMPK and Bcl-2 decreased and the expression of p-mTORCl, p-p70S6K, Bax and cleaved caspase-3 increased when PA (0.4 mmol • L"1) stimulated cells for 24 h compared with control group. Resveratrol pre-treatment could significantly reverse the above chan-ges. Conclusions Resveratrol can significantly inhibit the apoptosis of cardiomyocytes induced by high fat. Its mechanism may be related to the regulation of AMPK/mTORCl/p70S6K signaling pathway.
RESUMO
Macroautophagy is a catabolic pathway that degrades cellular components through the lysosomal machinery. Autophagy acts as a survival mechanism under energy depletion-or nutrition deficiency-caused stress as an intracellular quality management system by clearing damaged organelles like mitochondria and proteins. During the early and late stages of cancer development, the role of autophagy differs. In the very early stages of carcinogenesis, autophagy has an important function by reducing cancer initiating genetic instability and aberrant protein aggregates as well as promoting anti-cancer immune response. In established malignant tumors autophagy confers resistance against metabolic stress caused by nutrient deprivation and the rapid proliferation of carcinoma cells. This function of autophagy is also important for radiation and chemotherapy resistance in cancer. Autophagy not only promotes the survival of tumor cells but also in special condition leads to autophagic tumor cell death. During dysfunctional apoptosis this form of cell death mainly sensitizes cancer cells for therapy such as ionizing radiation. Therefore, the functions of autophagy during cancer progression and therapy are two-sided and further research is needed to understand them in greater detail. In this review the regulation and the role of autophagy in cancer and chemotherapy resistance are discussed.