Abstract
25-hydroxycholesterol (25-HC) is an oxysterol synthesized from cholesterol by cholesterol-25-hydroxylase during cholesterol metabolism. The aim of this study was to verify whether 25-HC induces oxiapoptophagy in fibroblasts. 25-HC not only decreased the survival of L929 cells, but also increased the number of cells with condensed chromatin and altered morphology. Fluorescence-activated cell sorting results showed that there was a dose-dependent increase in the apoptotic populations of L929 cells upon treatment with 25-HC. 25-HC-induced apoptotic cell death was mediated by the death receptor-dependent extrinsic and mitochondria-dependent intrinsic apoptosis pathway, through the cascade activation of caspases including caspase-8, -9, and -3 in L929 cells. There was an increase in the levels of reactive oxygen species and inflammatory mediators such as inducible nitric oxide synthase, cyclooxygenase-2, nitric oxide, and prostaglandin E2 in L929 cells treated with 25-HC. Moreover, 25-HC caused an increase in the expression of beclin-1 and microtubule-associated protein 1A/1B-light chain 3, an autophagy biomarker, in L929 cells. There was a significant decrease in the phosphorylation of protein kinase B (Akt) in L929 cells treated with 25-HC. Taken together, 25-HC induced oxiapoptophagy through the modulation of Akt and p53 cellular signaling pathways in L929 cells.
Highlights
Cholesterol is a lipid sterol that serves as an essential molecule for the survival and growth of mammalian cells, and as a precursor of bile acids, sterol hormones, and vitamin D, which are implicated in cell signaling processes [1]
Oxysterols are oxidized derivatives of cholesterol that are generated by means of Oxysterols are oxidized derivatives of cholesterol that are generated by means of auto-oxidation by free radicals and reactive oxygen species (ROS), or formed enzymatically auto-oxidation by free radicals and reactive oxygen species (ROS), or formed enzymatithrough a variety of enzymes that are involved in the synthesis of bile acid [14]
We investigated 25-HC25-HC-induced oxiapoptophagy, a type of cell death associated with oxidative stress, induced oxiapoptophagy, a type of cell death associated with oxidative stress, apoptosis, apoptosis, and autophagy mediated by oxysterol, and its underlying cellular signaling and autophagy mediated by oxysterol, and its underlying cellular signaling pathways in pathways in L929 mouse fibroblast cells
Summary
Cholesterol is a lipid sterol that serves as an essential molecule for the survival and growth of mammalian cells, and as a precursor of bile acids, sterol hormones, and vitamin D, which are implicated in cell signaling processes [1]. Cholesterol homeostasis in both cellular and systemic concentrations is precisely regulated by the synthesis and transport systems in mammalian cells [2]. Oxysterols are oxidized derivatives of cholesterol that are generated by means of Oxysterols are oxidized derivatives of cholesterol that are generated by means of auto-oxidation by free radicals and reactive oxygen species (ROS), or formed enzymatically auto-oxidation by free radicals and reactive oxygen species (ROS), or formed enzymatithrough a variety of enzymes that are involved in the synthesis of bile acid [14]. Altoxysterols generally existexist at very lowlow concentrations hough oxysterols generally at very concentrationsininvivo, vivo,they theyplay play aa key key role role in various functions, including development, regulation of immune cell inphysiological various physiological functions, including development, regulation of immunecell cellresponses, remetabolism, and cell survival
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