Up-regulation of mitochondrial transcription factor 1 mRNA levels by GH in VSMC

Life Sci. 2004 Mar 12;74(17):2097-109. doi: 10.1016/j.lfs.2003.07.057.

Abstract

It is well known that growth hormone (GH) is involved in the development of arteriosclerosis in which vascular smooth muscle cells (VSMC) play an important role. In this study, we attempted to specify the genes up- or down-regulated by recombinant human GH (rhGH) in VSMC using a differential display method. We found that rhGH increased cytochrome oxidase subunit II/III mRNA in VSMC. Furthermore, the mRNA for mitochondrial transcription factor 1 (mtTF1), which stimulates the expression of cytochrome oxidase subunit II/III, was found to be up-regulated by rhGH in a dose dependent manner using a quantitative PCR method. On the other hand, IGF-I alone did not change mtTF1 mRNA levels. In rat L6 myoblasts and rat H4-II-E hepatocytes, rhGH did not change mtTF1 mRNA levels. Pretreatment with a JAK2 inhibitor AG490 (10 nM) and a MEK inhibitor PD98059 (10 microM) suppressed rhGH-induced rise in mtTF1 mRNA levels of VSMC to the control levels. Pretreatment with a PI-3kinase inhibitor wortomannin (1 nM) did not suppress rhGH-induced rise in mtTF1 mRNA levels. These findings suggest that GH up-regulates mtTF1 mRNA levels through JAK2 and MEK signaling in VSMC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androstadienes / pharmacology
  • Animals
  • Cell Line, Tumor
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Dose-Response Relationship, Drug
  • Electron Transport Complex IV / biosynthesis
  • Enzyme Inhibitors / pharmacology
  • Female
  • Flavonoids / pharmacology
  • Gene Expression Profiling
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Human Growth Hormone / pharmacology*
  • Humans
  • Insulin-Like Growth Factor I / pharmacology
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / metabolism
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • RNA / analysis
  • RNA, Messenger* / metabolism
  • RNA, Mitochondrial
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tyrphostins / pharmacology
  • Up-Regulation / drug effects*
  • Wortmannin

Substances

  • Androstadienes
  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • Flavonoids
  • Mitochondrial Proteins
  • Nuclear Proteins
  • RNA, Messenger
  • RNA, Mitochondrial
  • TFAM protein, human
  • Tfam protein, rat
  • Transcription Factors
  • Tyrphostins
  • alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide
  • mitochondrial transcription factor A
  • Human Growth Hormone
  • RNA
  • Insulin-Like Growth Factor I
  • Electron Transport Complex IV
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
  • Wortmannin