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AICAR-induced activation of AMPK negatively regulates myotube hypertrophy through the HSP72-mediated pathway in C2C12 skeletal muscle cells.
Am J Physiol Endocrinol Metab. 2014 Feb; 306(3):E344-54.AJ

Abstract

5'-AMP-activated protein kinase (AMPK) plays an important role as a negative regulator of skeletal muscle mass. However, the precise mechanism of AMPK-mediated regulation of muscle mass is not fully clarified. Heat shock proteins (HSPs), stress-induced molecular chaperones, are related with skeletal muscle adaptation, but the association between AMPK and HSPs in skeletal muscle hypertrophy is unknown. Thus, we investigated whether AMPK regulates hypertrophy by mediating HSPs in C2C12 cells. The treatment with AICAR, a potent stimulator of AMPK, decreased 72-kDa HSP (HSP72) expression, whereas there were no changes in the expressions of 25-kDa HSP, 70-kDa heat shock cognate, and heat shock transcription factor 1 in myotubes. Protein content and diameter were less in the AICAR-treated myotubes in those without treatment. AICAR-induced suppression of myotube hypertrophy and HSP72 expression was attenuated in the siRNA-mediated AMPKα knockdown myotubes. AICAR increased microRNA (miR)-1, a modulator of HSP72, and the increase of miR-1 was not induced in AMPKα knockdown condition. Furthermore, siRNA-mediated HSP72 knockdown blocked AICAR-induced inhibition of myotube hypertrophy. AICAR upregulated the gene expression of muscle Ring-finger 1, and this alteration was suppressed in either AMPKα or HSP72 knockdown myotubes. The phosphorylation of p70 S6 kinase Thr(389) was downregulated by AICAR, whereas this was attenuated in AMPKα, but not in HSP72, knockdown myotubes. These results suggest that AMPK inhibits hypertrophy through, in part, an HSP72-associated mechanism via miR-1 and protein degradation pathways in skeletal muscle cells.

Authors+Show Affiliations

Department of Physiology, Graduate School of Health Sciences, Toyohashi SOZO University, Toyohashi, Japan;No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24347059

Citation

Egawa, Tatsuro, et al. "AICAR-induced Activation of AMPK Negatively Regulates Myotube Hypertrophy Through the HSP72-mediated Pathway in C2C12 Skeletal Muscle Cells." American Journal of Physiology. Endocrinology and Metabolism, vol. 306, no. 3, 2014, pp. E344-54.
Egawa T, Ohno Y, Goto A, et al. AICAR-induced activation of AMPK negatively regulates myotube hypertrophy through the HSP72-mediated pathway in C2C12 skeletal muscle cells. Am J Physiol Endocrinol Metab. 2014;306(3):E344-54.
Egawa, T., Ohno, Y., Goto, A., Ikuta, A., Suzuki, M., Ohira, T., Yokoyama, S., Sugiura, T., Ohira, Y., Yoshioka, T., & Goto, K. (2014). AICAR-induced activation of AMPK negatively regulates myotube hypertrophy through the HSP72-mediated pathway in C2C12 skeletal muscle cells. American Journal of Physiology. Endocrinology and Metabolism, 306(3), E344-54. https://doi.org/10.1152/ajpendo.00495.2013
Egawa T, et al. AICAR-induced Activation of AMPK Negatively Regulates Myotube Hypertrophy Through the HSP72-mediated Pathway in C2C12 Skeletal Muscle Cells. Am J Physiol Endocrinol Metab. 2014;306(3):E344-54. PubMed PMID: 24347059.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - AICAR-induced activation of AMPK negatively regulates myotube hypertrophy through the HSP72-mediated pathway in C2C12 skeletal muscle cells. AU - Egawa,Tatsuro, AU - Ohno,Yoshitaka, AU - Goto,Ayumi, AU - Ikuta,Akihiro, AU - Suzuki,Miho, AU - Ohira,Tomotaka, AU - Yokoyama,Shingo, AU - Sugiura,Takao, AU - Ohira,Yoshinobu, AU - Yoshioka,Toshitada, AU - Goto,Katsumasa, Y1 - 2013/12/17/ PY - 2013/12/19/entrez PY - 2013/12/19/pubmed PY - 2014/4/1/medline KW - acetyl-CoA carboxylase KW - atrogin-1 KW - heat shock transcription factor 1 KW - microRNA KW - muscle rRing-finger 1 SP - E344 EP - 54 JF - American journal of physiology. Endocrinology and metabolism JO - Am J Physiol Endocrinol Metab VL - 306 IS - 3 N2 - 5'-AMP-activated protein kinase (AMPK) plays an important role as a negative regulator of skeletal muscle mass. However, the precise mechanism of AMPK-mediated regulation of muscle mass is not fully clarified. Heat shock proteins (HSPs), stress-induced molecular chaperones, are related with skeletal muscle adaptation, but the association between AMPK and HSPs in skeletal muscle hypertrophy is unknown. Thus, we investigated whether AMPK regulates hypertrophy by mediating HSPs in C2C12 cells. The treatment with AICAR, a potent stimulator of AMPK, decreased 72-kDa HSP (HSP72) expression, whereas there were no changes in the expressions of 25-kDa HSP, 70-kDa heat shock cognate, and heat shock transcription factor 1 in myotubes. Protein content and diameter were less in the AICAR-treated myotubes in those without treatment. AICAR-induced suppression of myotube hypertrophy and HSP72 expression was attenuated in the siRNA-mediated AMPKα knockdown myotubes. AICAR increased microRNA (miR)-1, a modulator of HSP72, and the increase of miR-1 was not induced in AMPKα knockdown condition. Furthermore, siRNA-mediated HSP72 knockdown blocked AICAR-induced inhibition of myotube hypertrophy. AICAR upregulated the gene expression of muscle Ring-finger 1, and this alteration was suppressed in either AMPKα or HSP72 knockdown myotubes. The phosphorylation of p70 S6 kinase Thr(389) was downregulated by AICAR, whereas this was attenuated in AMPKα, but not in HSP72, knockdown myotubes. These results suggest that AMPK inhibits hypertrophy through, in part, an HSP72-associated mechanism via miR-1 and protein degradation pathways in skeletal muscle cells. SN - 1522-1555 UR - https://www.unboundmedicine.com/medline/citation/24347059/AICAR_induced_activation_of_AMPK_negatively_regulates_myotube_hypertrophy_through_the_HSP72_mediated_pathway_in_C2C12_skeletal_muscle_cells_ L2 - https://journals.physiology.org/doi/10.1152/ajpendo.00495.2013?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -