Tags

Type your tag names separated by a space and hit enter

The deacetylase enzyme SIRT1 is not associated with oxidative capacity in rat heart and skeletal muscle and its overexpression reduces mitochondrial biogenesis.
J Physiol 2009; 587(Pt 8):1817-28JP

Abstract

Deacetylation of PGC-1alpha by SIRT1 is thought to be an important step in increasing PGC-1alpha transcriptional activity, since in muscle cell lines SIRT1 induces PGC-1alpha protein expression and mitochondrial biogenesis. We examined the relationship between SIRT1 protein and activity, PGC-1alpha and markers of mitochondrial density, (a) across a range of metabolically heterogeneous skeletal muscles and the heart, and when mitochondrial biogenesis was stimulated by (b) chronic muscle stimulation (7 days) and (c) AICAR administration (5 days), and finally, (d) we also examined the effects of SIRT1 overexpression on mitochondrial biogenesis and PGC-1alpha. SIRT1 protein and activity were correlated (r = 0.97). There were negative correlations between SIRT1 protein and PGC-1alpha (r = -0.95), COX IV (r = -0.94) and citrate synthase (r = -0.97). Chronic muscle stimulation and AICAR upregulated PGC-1alpha protein (22-159%) and oxidative capacity (COX IV, 20-69%); in each instance SIRT1 protein was downregulated by 20-40%, while SIRT1 intrinsic activity was increased. SIRT1 overexpression in rodent muscle increased SIRT1 protein (+240%) and doubled SIRT1 activity, but PGC-1alpha (-25%), mtTFA (-14%) and COX IV (-10%) proteins were downregulated. Taken altogether these experiments are not consistent with the notion that SIRT1 protein plays an obligatory regulatory role in the process of PGC-1alpha-mediated mitochondrial biogenesis in mammalian muscle.

Authors+Show Affiliations

Department of Human Health and Nutritional Science, University of Guelph, Guelph, Ontario, Canada, N1G 2W1.No 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

19237425

Citation

Gurd, Brendon J., et al. "The Deacetylase Enzyme SIRT1 Is Not Associated With Oxidative Capacity in Rat Heart and Skeletal Muscle and Its Overexpression Reduces Mitochondrial Biogenesis." The Journal of Physiology, vol. 587, no. Pt 8, 2009, pp. 1817-28.
Gurd BJ, Yoshida Y, Lally J, et al. The deacetylase enzyme SIRT1 is not associated with oxidative capacity in rat heart and skeletal muscle and its overexpression reduces mitochondrial biogenesis. J Physiol (Lond). 2009;587(Pt 8):1817-28.
Gurd, B. J., Yoshida, Y., Lally, J., Holloway, G. P., & Bonen, A. (2009). The deacetylase enzyme SIRT1 is not associated with oxidative capacity in rat heart and skeletal muscle and its overexpression reduces mitochondrial biogenesis. The Journal of Physiology, 587(Pt 8), pp. 1817-28. doi:10.1113/jphysiol.2008.168096.
Gurd BJ, et al. The Deacetylase Enzyme SIRT1 Is Not Associated With Oxidative Capacity in Rat Heart and Skeletal Muscle and Its Overexpression Reduces Mitochondrial Biogenesis. J Physiol (Lond). 2009 Apr 15;587(Pt 8):1817-28. PubMed PMID: 19237425.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The deacetylase enzyme SIRT1 is not associated with oxidative capacity in rat heart and skeletal muscle and its overexpression reduces mitochondrial biogenesis. AU - Gurd,Brendon J, AU - Yoshida,Yuko, AU - Lally,James, AU - Holloway,Graham P, AU - Bonen,Arend, Y1 - 2009/02/23/ PY - 2009/2/25/entrez PY - 2009/2/25/pubmed PY - 2009/7/16/medline SP - 1817 EP - 28 JF - The Journal of physiology JO - J. Physiol. (Lond.) VL - 587 IS - Pt 8 N2 - Deacetylation of PGC-1alpha by SIRT1 is thought to be an important step in increasing PGC-1alpha transcriptional activity, since in muscle cell lines SIRT1 induces PGC-1alpha protein expression and mitochondrial biogenesis. We examined the relationship between SIRT1 protein and activity, PGC-1alpha and markers of mitochondrial density, (a) across a range of metabolically heterogeneous skeletal muscles and the heart, and when mitochondrial biogenesis was stimulated by (b) chronic muscle stimulation (7 days) and (c) AICAR administration (5 days), and finally, (d) we also examined the effects of SIRT1 overexpression on mitochondrial biogenesis and PGC-1alpha. SIRT1 protein and activity were correlated (r = 0.97). There were negative correlations between SIRT1 protein and PGC-1alpha (r = -0.95), COX IV (r = -0.94) and citrate synthase (r = -0.97). Chronic muscle stimulation and AICAR upregulated PGC-1alpha protein (22-159%) and oxidative capacity (COX IV, 20-69%); in each instance SIRT1 protein was downregulated by 20-40%, while SIRT1 intrinsic activity was increased. SIRT1 overexpression in rodent muscle increased SIRT1 protein (+240%) and doubled SIRT1 activity, but PGC-1alpha (-25%), mtTFA (-14%) and COX IV (-10%) proteins were downregulated. Taken altogether these experiments are not consistent with the notion that SIRT1 protein plays an obligatory regulatory role in the process of PGC-1alpha-mediated mitochondrial biogenesis in mammalian muscle. SN - 1469-7793 UR - https://www.unboundmedicine.com/medline/citation/19237425/The_deacetylase_enzyme_SIRT1_is_not_associated_with_oxidative_capacity_in_rat_heart_and_skeletal_muscle_and_its_overexpression_reduces_mitochondrial_biogenesis_ L2 - https://doi.org/10.1113/jphysiol.2008.168096 DB - PRIME DP - Unbound Medicine ER -