7-ketocholesterol Induces Apoptosis of MC3T3-E1 Cells Associated with Reactive Oxygen Species Generation, Endoplasmic Reticulum Stress and Caspase-3/7 Dependent Pathway

Overview

Journal Mol Genet Metab Rep

Specialty Endocrinology

Date 2017 Jan 25

PMID 28116245

Citations 8

Authors

Yuta Sato

Noriko Ishihara

Daiji Nagayama

Atsuhito Saiki

Ichiro Tatsuno

Affiliations

Soon will be listed here.

Abstract

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of bone fractures without reduction of bone mineral density. The cholesterol oxide 7-ketocholesterol (7KCHO) has been implicated in numerous diseases such as atherosclerosis, Alzheimer's disease, Parkinson's disease, cancer, age-related macular degeneration and T2DM. In the present study, 7KCHO decreased the viability of MC3T3-E1 cells, increased reactive oxygen species (ROS) production and apoptotic rate, and upregulated the caspase-3/7 pathway. Furthermore, these effects of 7KCHO were abolished by pre-incubation of the cells with -acetylcysteine (NAC), an ROS inhibitor. Also, 7KCHO enhanced the mRNA expression of two endoplasmic reticulum (ER) stress markers; CHOP and GRP78, in MC3T3-E1 cells. Pre-incubation of the cells with NAC suppressed the 7KCHO-induced upregulation of CHOP, but not GRP78. In conclusion, we demonstrated that 7KCHO induced apoptosis of MC3T3-E1 cells associated with ROS generation, ER stress, and caspase-3/7 activity, and the effects of 7KCHO were abolished by the ROS inhibitor NAC. These findings may provide new insight into the relationship between oxysterol and pathophysiology of osteoporosis seen in T2DM.

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