PMID: 9661807Jul 14, 1998Paper

Mechanical stretch activates a pathway linked to mevalonate metabolism in cultured neonatal rat heart cells

Hypertension Research : Official Journal of the Japanese Society of Hypertension
Y KashiwagiK Kikuchi

Abstract

It is not certain whether activation of the Ras/mitogen-activated protein (MAP) kinase pathway is involved in cardiac hypertrophy. 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, such as lovastatin, prevent farnesylation of the Ras protein, which is critical for Ras's membrane localization and function. Therefore, the present study was undertaken to investigate the role of the Ras pathway, which is linked to mevalonate metabolism, in the mechanism of stretch-induced myocyte hypertrophy. Myocytes isolated from 1- to 2-day-old rats were cultured at 4.1 x 10(6) cells per well in a deformable silicon dish and incubated with serum-free medium for 7 days. The cultures were stretched by 15% on culture day 4. Stretch increased the RNA/DNA ratio by 20% to 26% on culture days 5 and 6 and the protein/DNA ratio by 18% to 20% on culture days 6 and 7. Stretch accelerated rates of protein synthesis by 24% on culture day 6. Stretch increased protein kinase C (PKC) activity, MAP kinase activity, and c-fos mRNA expression. A selective PKC inhibitor, calphostin C (1 x 10(-6) M), prevented the stretch-induced increase in PKC activity, but lovastatin (7.5 x 10(-6) M) did not. Lovastatin as well as calphostin C partially but si...Continue Reading

Citations

Jul 25, 2007·Cardiovascular Toxicology·Simon W RabkinJennifer Y Kong
Mar 4, 2006·Biochemical and Biophysical Research Communications·Astrid LiedertAnita Ignatius
Jun 27, 2000·The Anatomical Record·R J Tomanek, G C Schatteman
Jan 22, 2010·Molecular and Cellular Biochemistry·Nitin Mahajan, Veena Dhawan
Feb 13, 2001·American Journal of Physiology. Heart and Circulatory Physiology·W ZhengR J Tomanek

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