%0 Journal Article
%T Pathway of Programmed Cell Death and Oxidative Stress Induced by ¦Â-Hydroxybutyrate in Dairy Cow Abomasum Smooth Muscle Cells and in Mouse Gastric Smooth Muscle
%A Wulin Tian
%A Teng Wei
%A Bin Li
%A Zhe Wang
%A Naisheng Zhang
%A Guanghong Xie
%J PLOS ONE
%D 2014
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0096775
%X The administration of exogenous ¦Â-hydroxybutyrate (¦Â-HB), as well as fasting and caloric restriction, is a condition associated with ¦Â-HB abundance and decreased appetite in animals. Increased ¦Â-HB and decreased appetite exist simultaneously in some diseases, such as bovine left displaced abomasums (LDA) and human chronic gastritis. However, the effects of ¦Â-HB on stomach injuries have not been explored. To elucidate the possible effects of exogenous ¦Â-HB on the stomach, mice were injected intraperitoneally with ¦Â-HB, and bovine abomasum smooth muscle cells (BSMCs) were treated with different concentrations of ¦Â-HB. We found that ¦Â-HB induced BSMCs endoplasmic reticulum- and mitochondria-mediated apoptotic cell death. ¦Â-HB promoted Bax expression and caspase-12, -9, and -3 activation while blocking Bcl-2 expression. ¦Â-HB also promoted AIF, EndoG release and p53 expression. ¦Â-HB acted on key molecules in the apoptotic cell death pathway and increased p38 and c-June NH2-terminal kinase phosphorylation while inhibiting ERK phosphorylation and PCNA expression. ¦Â-HB upregulated P27 and P21 mRNA levels while downregulating cyclin and CDK mRNA levels, arresting the cell cycle. These results suggest that BSMCs treated with ¦Â-HB can induce oxidative stress, which can be prevented by intracellular calcium chelators BAPTA/AM but not antioxidant NAC. Additionally, these results suggest that ¦Â-HB causes ROS generation through a Ca2+-dependent mechanism and that intracellular Ca2+ levels play a critical role in ¦Â-HB -induced apoptotic cell death. The impact of ¦Â-HB on programmed cell death and oxidative stress in vivo was confirmed in murine experiments. For the first time, we show oxidative stress effects of ¦Â-HB on smooth muscle. We propose that ¦Â-HB is a possible cause of some stomach diseases, including bovine LDA.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0096775