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Nuclear SIRT1 activity, but not protein content, regulates mitochondrial biogenesis in rat and human skeletal muscle.

Abstract

Silent mating type information regulator 2 homolog 1 (SIRT1)-mediated peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) deacetylation is potentially key for activating mitochondrial biogenesis. Yet, at the whole muscle level, SIRT1 is not associated with mitochondrial biogenesis (Gurd, BJ, Yoshida Y, Lally J, Holloway GP, Bonen A. J Physiol 587: 1817-1828, 2009). Therefore, we examined nuclear SIRT1 protein and activity in muscle with varied mitochondrial content and in response to acute exercise. We also measured these parameters after stimulating mitochondrial biogenesis with chronic muscle contraction and 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) administration in rodents and exercise training in humans. In skeletal and heart muscles, nuclear SIRT1 protein was negatively correlated with indices of mitochondrial density (citrate synthase activity, CS; cytochrome oxidase IV, COX IV), but SIRT1 activity was positively correlated with these parameters (r > 0.98). Acute exercise did not alter nuclear SIRT1 protein but did induce a time-dependent increase in nuclear SIRT1 activity. This increase in SIRT1 activity was temporally related to increases in mRNA expression of genes activated by PGC-1α. Both chronic muscle stimulation and AICAR increased mitochondrial biogenesis and muscle PGC-1α, but not nuclear PGC-1α. Concomitantly, muscle and nuclear SIRT1 protein contents were reduced, but nuclear SIRT1 activity was increased. In human muscle, training-induced mitochondrial biogenesis did not alter muscle or nuclear SIRT1 protein content, but it did increase muscle and nuclear PGC-1α and SIRT1 activity. Thus, nuclear SIRT1 activity, but not muscle or nuclear SIRT1 protein content, is associated with contraction-stimulated mitochondrial biogenesis in rat and human muscle, possibly via AMPK activation.

Authors+Show Affiliations

School of Kinesiology and Health Studies, Queen's University, Kingston, Canada. gurdb@queensu.caNo 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

21543634

Citation

Gurd, Brendon J., et al. "Nuclear SIRT1 Activity, but Not Protein Content, Regulates Mitochondrial Biogenesis in Rat and Human Skeletal Muscle." American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, vol. 301, no. 1, 2011, pp. R67-75.
Gurd BJ, Yoshida Y, McFarlan JT, et al. Nuclear SIRT1 activity, but not protein content, regulates mitochondrial biogenesis in rat and human skeletal muscle. Am J Physiol Regul Integr Comp Physiol. 2011;301(1):R67-75.
Gurd, B. J., Yoshida, Y., McFarlan, J. T., Holloway, G. P., Moyes, C. D., Heigenhauser, G. J., ... Bonen, A. (2011). Nuclear SIRT1 activity, but not protein content, regulates mitochondrial biogenesis in rat and human skeletal muscle. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 301(1), pp. R67-75. doi:10.1152/ajpregu.00417.2010.
Gurd BJ, et al. Nuclear SIRT1 Activity, but Not Protein Content, Regulates Mitochondrial Biogenesis in Rat and Human Skeletal Muscle. Am J Physiol Regul Integr Comp Physiol. 2011;301(1):R67-75. PubMed PMID: 21543634.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nuclear SIRT1 activity, but not protein content, regulates mitochondrial biogenesis in rat and human skeletal muscle. AU - Gurd,Brendon J, AU - Yoshida,Yuko, AU - McFarlan,Jay T, AU - Holloway,Graham P, AU - Moyes,Chris D, AU - Heigenhauser,George J F, AU - Spriet,Lawrence, AU - Bonen,Arend, Y1 - 2011/05/04/ PY - 2011/5/6/entrez PY - 2011/5/6/pubmed PY - 2011/9/9/medline SP - R67 EP - 75 JF - American journal of physiology. Regulatory, integrative and comparative physiology JO - Am. J. Physiol. Regul. Integr. Comp. Physiol. VL - 301 IS - 1 N2 - Silent mating type information regulator 2 homolog 1 (SIRT1)-mediated peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) deacetylation is potentially key for activating mitochondrial biogenesis. Yet, at the whole muscle level, SIRT1 is not associated with mitochondrial biogenesis (Gurd, BJ, Yoshida Y, Lally J, Holloway GP, Bonen A. J Physiol 587: 1817-1828, 2009). Therefore, we examined nuclear SIRT1 protein and activity in muscle with varied mitochondrial content and in response to acute exercise. We also measured these parameters after stimulating mitochondrial biogenesis with chronic muscle contraction and 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) administration in rodents and exercise training in humans. In skeletal and heart muscles, nuclear SIRT1 protein was negatively correlated with indices of mitochondrial density (citrate synthase activity, CS; cytochrome oxidase IV, COX IV), but SIRT1 activity was positively correlated with these parameters (r > 0.98). Acute exercise did not alter nuclear SIRT1 protein but did induce a time-dependent increase in nuclear SIRT1 activity. This increase in SIRT1 activity was temporally related to increases in mRNA expression of genes activated by PGC-1α. Both chronic muscle stimulation and AICAR increased mitochondrial biogenesis and muscle PGC-1α, but not nuclear PGC-1α. Concomitantly, muscle and nuclear SIRT1 protein contents were reduced, but nuclear SIRT1 activity was increased. In human muscle, training-induced mitochondrial biogenesis did not alter muscle or nuclear SIRT1 protein content, but it did increase muscle and nuclear PGC-1α and SIRT1 activity. Thus, nuclear SIRT1 activity, but not muscle or nuclear SIRT1 protein content, is associated with contraction-stimulated mitochondrial biogenesis in rat and human muscle, possibly via AMPK activation. SN - 1522-1490 UR - https://www.unboundmedicine.com/medline/citation/21543634/Nuclear_SIRT1_activity_but_not_protein_content_regulates_mitochondrial_biogenesis_in_rat_and_human_skeletal_muscle_ L2 - http://www.physiology.org/doi/full/10.1152/ajpregu.00417.2010?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -