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Author Hao, Yuhui ♦ Liu, Cong ♦ Huang, Jiawei ♦ Gu, Ying ♦ Li, Hong ♦ Yang, Zhangyou ♦ Liu, Jing ♦ Wang, Weidong ♦ Li, Rong
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ APOPTOSIS ♦ CONNECTIVE TISSUE CELLS ♦ CYTOCHROMES ♦ DMSO ♦ GLUTATHIONE ♦ IODIDES ♦ MITOCHONDRIA ♦ OXIDATION ♦ PHOSPHOTRANSFERASES ♦ RECEPTORS ♦ RNA ♦ SKELETON ♦ STH ♦ THERAPY
Abstract Depleted uranium (DU) mainly accumulates in the bone over the long term. Osteoblast cells are responsible for the formation of bone, and they are sensitive to DU damage. However, studies investigating methods of reducing DU damage in osteoblasts are rarely reported. Ghrelin is a stomach hormone that stimulates growth hormones released from the hypothalamic–pituitary axis, and it is believed to play an important physiological role in bone metabolism. This study evaluates the impact of ghrelin on DU-induced apoptosis of the osteoblast MC3T3-E1 and investigates its underlying mechanisms. The results show that ghrelin relieved the intracellular oxidative stress induced by DU, eliminated reactive oxygen species (ROS) and reduced lipid peroxidation by increasing intracellular GSH levels; in addition, ghrelin effectively suppressed apoptosis, enhanced mitochondrial membrane potential, and inhibited cytochrome c release and caspase-3 activation after DU exposure. Moreover, ghrelin significantly reduced the expression of DU-induced phosphorylated p38-mitogen-activated protein kinase (MAPK). A specific inhibitor (SB203580) or specific siRNA of p38-MAPK could significantly suppress DU-induced apoptosis and related signals, whereas ROS production was not affected. In addition, ghrelin receptor inhibition could reduce the anti-apoptosis effect of ghrelin on DU and reverse the effect of ghrelin on intracellular ROS and p38-MAPK after DU exposure. These results suggest that ghrelin can suppress DU-induced apoptosis of MC3T3-E1 cells, reduce DU-induced oxidative stress by interacting with its receptor, and inhibit downstream p38-MAPK activation, thereby suppressing the mitochondrial-dependent apoptosis pathway. - Highlights: • Ghrelin suppressed DU-induced apoptosis of MC3T3-E1 cells. • Ghrelin inhibited DU-induced oxidative stress and further p38-MAPK activation. • Ghrelin further suppressed mitochondrial-dependent apoptosis pathway. • The anti-oxidation effect of ghrelin was regulated through its receptor. • Ghrelin has the potential for use in drug therapies for DU poisoning.
ISSN 0041008X
Educational Use Research
Learning Resource Type Article
Publisher Date 2016-01-01
Publisher Place United States
Journal Toxicology and Applied Pharmacology
Volume Number 290


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