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Isoform-specific increases in murine skeletal muscle peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) mRNA in response to beta2-adrenergic receptor activation and exercise.
Endocrinology. 2008 Sep; 149(9):4527-33.E

Abstract

Adrenergic receptor (AR) activation increases expression of peroxisome proliferator-activated receptor (PPAR)-gamma coactivator 1alpha (PGC-1alpha) mRNA, which may promote mitochondrial biogenesis in skeletal muscles. An AR-activated increase in PGC-1alpha mRNA was observed in exercise. PGC-1alpha mRNA is considered a single transcript (PGC-1alpha-a); however, a transcript search of PGC-1alpha in expressed sequence tag libraries revealed that two novel isoforms of PGC-1alpha mRNA, named PGC-1alpha-b and PGC-1alpha-c, were expressed in mice tissues. Compared with PGC-1alpha-a mRNA (a previously described isoform), PGC-1alpha-b or PGC-1alpha-c mRNA was transcribed by a different exon 1 of the PGC-1alpha gene and produced slightly smaller-sized proteins. PGC-1alpha-b or PGC-1alpha-c protein was functional; both isoforms possessed transcriptional activity and could coactivate PPARs, similar to those in PGC-1alpha-a in vitro. Transgenic mice overexpressing PGC-1alpha-b or PGC-1alpha-c in skeletal muscles showed increased gene expression related to mitochondrial biogenesis and fatty acid oxidation. In C57BL/6J mice, injection of the beta2-AR agonist clenbuterol increased PGC-1alpha-b and PGC-1alpha-c mRNA expression more than 350-fold, but not PGC-1alpha-a, in skeletal muscle. A single bout of exercise also increased PGC-1alpha-b and PGC-1alpha-c mRNAs, but not PGC-1alpha-a, in skeletal muscles. The increases in skeletal muscles in response to exercise were inhibited by pretreatment with the beta2-AR-specific inhibitor ICI 118,551. However, in liver, fasting increased PGC-1alpha-a mRNA, but not PGC-1alpha-b and PGC-1alpha-c mRNAs. These data indicate that AR activation is a major mechanism of an increase in PGC-1alpha expression in skeletal muscles, and the increase in PGC-1alpha mRNAs was isoform specific.

Authors+Show Affiliations

National Institute of Health and Nutrition, Tokyo 162-8636, Japan. shinjim@nih.go.jpNo 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

18511502

Citation

Miura, Shinji, et al. "Isoform-specific Increases in Murine Skeletal Muscle Peroxisome Proliferator-activated Receptor-gamma Coactivator-1alpha (PGC-1alpha) mRNA in Response to Beta2-adrenergic Receptor Activation and Exercise." Endocrinology, vol. 149, no. 9, 2008, pp. 4527-33.
Miura S, Kai Y, Kamei Y, et al. Isoform-specific increases in murine skeletal muscle peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) mRNA in response to beta2-adrenergic receptor activation and exercise. Endocrinology. 2008;149(9):4527-33.
Miura, S., Kai, Y., Kamei, Y., & Ezaki, O. (2008). Isoform-specific increases in murine skeletal muscle peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) mRNA in response to beta2-adrenergic receptor activation and exercise. Endocrinology, 149(9), 4527-33. https://doi.org/10.1210/en.2008-0466
Miura S, et al. Isoform-specific Increases in Murine Skeletal Muscle Peroxisome Proliferator-activated Receptor-gamma Coactivator-1alpha (PGC-1alpha) mRNA in Response to Beta2-adrenergic Receptor Activation and Exercise. Endocrinology. 2008;149(9):4527-33. PubMed PMID: 18511502.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Isoform-specific increases in murine skeletal muscle peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) mRNA in response to beta2-adrenergic receptor activation and exercise. AU - Miura,Shinji, AU - Kai,Yuko, AU - Kamei,Yasutomi, AU - Ezaki,Osamu, Y1 - 2008/05/29/ PY - 2008/5/31/pubmed PY - 2008/10/3/medline PY - 2008/5/31/entrez SP - 4527 EP - 33 JF - Endocrinology JO - Endocrinology VL - 149 IS - 9 N2 - Adrenergic receptor (AR) activation increases expression of peroxisome proliferator-activated receptor (PPAR)-gamma coactivator 1alpha (PGC-1alpha) mRNA, which may promote mitochondrial biogenesis in skeletal muscles. An AR-activated increase in PGC-1alpha mRNA was observed in exercise. PGC-1alpha mRNA is considered a single transcript (PGC-1alpha-a); however, a transcript search of PGC-1alpha in expressed sequence tag libraries revealed that two novel isoforms of PGC-1alpha mRNA, named PGC-1alpha-b and PGC-1alpha-c, were expressed in mice tissues. Compared with PGC-1alpha-a mRNA (a previously described isoform), PGC-1alpha-b or PGC-1alpha-c mRNA was transcribed by a different exon 1 of the PGC-1alpha gene and produced slightly smaller-sized proteins. PGC-1alpha-b or PGC-1alpha-c protein was functional; both isoforms possessed transcriptional activity and could coactivate PPARs, similar to those in PGC-1alpha-a in vitro. Transgenic mice overexpressing PGC-1alpha-b or PGC-1alpha-c in skeletal muscles showed increased gene expression related to mitochondrial biogenesis and fatty acid oxidation. In C57BL/6J mice, injection of the beta2-AR agonist clenbuterol increased PGC-1alpha-b and PGC-1alpha-c mRNA expression more than 350-fold, but not PGC-1alpha-a, in skeletal muscle. A single bout of exercise also increased PGC-1alpha-b and PGC-1alpha-c mRNAs, but not PGC-1alpha-a, in skeletal muscles. The increases in skeletal muscles in response to exercise were inhibited by pretreatment with the beta2-AR-specific inhibitor ICI 118,551. However, in liver, fasting increased PGC-1alpha-a mRNA, but not PGC-1alpha-b and PGC-1alpha-c mRNAs. These data indicate that AR activation is a major mechanism of an increase in PGC-1alpha expression in skeletal muscles, and the increase in PGC-1alpha mRNAs was isoform specific. SN - 0013-7227 UR - https://www.unboundmedicine.com/medline/citation/18511502/Isoform_specific_increases_in_murine_skeletal_muscle_peroxisome_proliferator_activated_receptor_gamma_coactivator_1alpha__PGC_1alpha__mRNA_in_response_to_beta2_adrenergic_receptor_activation_and_exercise_ L2 - https://academic.oup.com/endo/article-lookup/doi/10.1210/en.2008-0466 DB - PRIME DP - Unbound Medicine ER -