β-Adrenergic stimulation does not activate p38 MAP kinase or induce PGC-1α in skeletal muscle

Sang Hyun Kim, Meiko Asaka, Kazuhiko Higashida, Yumiko Takahashi, John O. Holloszy, Dong Ho Han

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

There are reports that the β-adrenergic agonist clenbuterol induces a large increase in peroxisome proliferator-activated receptor-γ{phonetic} coactivator-1α (PGC-1α) in skeletal muscle. This has led to the hypothesis that the increases in PGC-1α and mitochondrial biogenesis induced in muscle by endurance exercise are mediated by catecholamines. In the present study, we evaluated this possibility and found that injecting rats with clenbuterol or norepinephrine induced large increases in PGC-1α and mitochondrial proteins in brown adipose tissue but had no effect on PGC-1α expression or mitochondrial biogenesis in skeletal muscle. In brown adipocytes, the increase in PGC-1α expression induced by β-adrenergic stimulation is mediated by activation of p38 mitogenactivated protein kinase (p38 MAPK), which phosphorylates and activates the cAMP response element binding protein (CREB) family member activating transcription factor 2 (ATF2), which binds to a cyclic AMP response element (CRE) in the PGC-1α promoter and mediates the increase in PGC-1α transcription. Phospho-CREB does not have this effect. Our results show that the reason for the lack of effect of β-adrenergic stimulation on PGC-1α expression in muscle is that catecholamines do not activate p38 or increase ATF2 phosphorylation in muscle.

Original languageEnglish
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume304
Issue number8
DOIs
Publication statusPublished - 2013 Apr 15

Fingerprint

p38 Mitogen-Activated Protein Kinases
Activating Transcription Factor 2
Adrenergic Agents
Clenbuterol
Cyclic AMP Response Element-Binding Protein
Skeletal Muscle
Organelle Biogenesis
Muscles
Catecholamines
Brown Adipocytes
Adrenergic Agonists
Peroxisome Proliferator-Activated Receptors
Phonetics
Brown Adipose Tissue
Mitochondrial Proteins
Response Elements
Cyclic AMP
Norepinephrine
Phosphorylation

Keywords

  • Brown fat
  • Clenbuterol
  • Mitochondria
  • Norepinephrine
  • Phospho-ATF2

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Endocrinology, Diabetes and Metabolism

Cite this

β-Adrenergic stimulation does not activate p38 MAP kinase or induce PGC-1α in skeletal muscle. / Kim, Sang Hyun; Asaka, Meiko; Higashida, Kazuhiko; Takahashi, Yumiko; Holloszy, John O.; Han, Dong Ho.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 304, No. 8, 15.04.2013.

Research output: Contribution to journalArticle

Kim, Sang Hyun ; Asaka, Meiko ; Higashida, Kazuhiko ; Takahashi, Yumiko ; Holloszy, John O. ; Han, Dong Ho. / β-Adrenergic stimulation does not activate p38 MAP kinase or induce PGC-1α in skeletal muscle. In: American Journal of Physiology - Endocrinology and Metabolism. 2013 ; Vol. 304, No. 8.
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