Retinoic Acid Leads to Cytoskeletal Rearrangement through AMPK-Rac1 and Stimulates Glucose Uptake through AMPK-p38 MAPK in Skeletal Muscle Cells

• Published in: The Journal of biological chemistry Vol. 283; no. 49; pp. 33969 - 33974
• Main Authors: Lee, Yun Mi, Lee, Jung Ok, Jung, Jin-Hee, Kim, Ji Hae, Park, Sun-Hwa, Park, Ji Man, Kim, Eung-Kyun, Suh, Pann-Ghill, Kim, Hyeon Soo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05.12.2008; American Society for Biochemistry and Molecular Biology
• Subjects: AMP-Activated Protein Kinases - metabolism; Animals; Biological Transport; Cofilin 1 - chemistry; Cyclin-Dependent Kinase Inhibitor p21 - metabolism; Cytoskeleton - metabolism; Glucose - metabolism; Mechanisms of Signal Transduction; Mice; Models, Biological; Muscle, Skeletal - cytology; Muscle, Skeletal - metabolism; Neuropeptides - metabolism; p38 Mitogen-Activated Protein Kinases - metabolism; Phosphorylation; rac GTP-Binding Proteins - metabolism; rac1 GTP-Binding Protein; RNA, Small Interfering - metabolism; Tretinoin - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M804469200

Retinoic acid (RA) is one of the major components of vitamin A. In the present study, we found that retinoic acid activated AMP-activated protein kinase (AMPK). RA induced Rac1-GTP formation and phosphorylation of its downstream target, p21-activated kinase (PAK), whereas the inhibition of AMPK blocked RA-induced Rac1 activation. Moreover, cofilin, an actin polymerization regulator, was activated when incubated with RA. We then showed that inhibition of AMPK by compound C, a selective inhibitor of AMPK, or small interfering RNA of AMPK α1 blocked RA-induced cofilin phosphorylation. Additionally, we found that retinoic acid-stimulated glucose uptake in differentiated C2C12 myoblast cells and activated p38 mitogen-activated protein kinase (MAPK). Finally, the inhibition of AMPK and p38 MAPK blocked retinoic acid-induced glucose uptake. In summary, our results suggest that retinoic acid may have cytoskeletal roles in skeletal muscle cells via stimulation of the AMPK-Rac1-PAK-cofillin pathway and may also have beneficial roles in glucose metabolism via stimulation of the AMPK-p38 MAPK pathway.