title: AMP-activated protein kinase α1 but not α2 catalytic subunit potentiates myogenin expression and myogenesis.
abstract: The link between AMP-activated protein kinase (AMPK) and myogenesis remains poorly defined. AMPK has two catalytic α subunits, α1 and α2. We postulated that AMPK promotes myogenesis in an isoform-specific manner. Primary myoblasts were prepared from AMPK knockout (KO) mice and AMPK conditional KO mice, and knockout of the α1 but not the α2 subunit resulted in downregulation of myogenin and reduced myogenesis. Myogenin expression and myogenesis were nearly abolished in the absence of both AMPKα1 and AMPKα2, while enhanced AMPK activity promoted myogenesis and myotube formation. The AMPKα1-specific effect on myogenesis was likely due to the dominant expression of α1 in myoblasts. These results were confirmed in C2C12 cells. To further evaluate the necessity of the AMPKα1 subunit for myogenesis in vivo, we prepared both DsRed AMPKα1 knockout myoblasts and enhanced green fluorescent protein (EGFP) wild-type myoblasts, which were cotransplanted into tibialis anterior muscle. A number of green fluorescent muscle fibers were observed, showing the fusion of engrafted wild-type myoblasts with muscle fibers; on the other hand, very few or no red muscle fibers were observed, indicating the absence of myogenic capacity of AMPKα1 knockout myoblasts. In summary, these results indicate that AMPK activity promotes myogenesis through a mechanism mediated by AMPKα1.
authors.affiliation: Department of Animal Sciences, Washington State University, Pullman, Washington, USA.
authors.forename: Xing
authors.initials: X
authors.lastname: Fu
authors.forename: Jun-Xing
authors.initials: JX
authors.lastname: Zhao
authors.forename: Mei-Jun
authors.initials: MJ
authors.lastname: Zhu
authors.forename: Marc
authors.initials: M
authors.lastname: Foretz
authors.forename: Benoit
authors.initials: B
authors.lastname: Viollet
authors.forename: Mike V
authors.initials: MV
authors.lastname: Dodson
authors.forename: Min
authors.initials: M
authors.lastname: Du
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D020134:Catalytic Domain; D002460:Cell Line; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024510:Muscle Development; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism; D018008:Myogenin / Q000235:genetics* / Q000378:metabolism
chemical_list: D018008:Myogenin; C548179:Prkaa1 protein, mouse; C534978:Prkaa2 protein, mouse; D055372:AMP-Activated Protein Kinases
references.citation: Am J Physiol Cell Physiol. 2012 Sep 1;303(5):C475-85
references.pmid: 22700795
references.citation: J Physiol. 2008 May 15;586(10):2651-64
references.pmid: 18372306
references.citation: Cell Calcium. 2011 Jul;50(1):73-83
references.pmid: 21641034
references.citation: Cell Calcium. 2013 Mar;53(3):217-23
references.pmid: 23298795
references.citation: Cell. 1997 Apr 4;89(1):139-48
references.pmid: 9094722
references.citation: Endocrinology. 2010 Jan;151(1):380-7
references.pmid: 19887565
references.citation: Biochem J. 2000 Mar 15;346 Pt 3:659-69
references.pmid: 10698692
references.citation: J Anim Sci. 1984 Dec;59(6):1651-6
references.pmid: 6543212
references.citation: Nutr Diabetes. 2011 May 16;1:e7
references.pmid: 23449382
references.citation: J Biol Chem. 2011 May 6;286(18):16426-34
references.pmid: 21454484
references.citation: Am J Pathol. 2012 Aug;181(2):583-92
references.pmid: 22683340
references.citation: Am J Physiol Endocrinol Metab. 2009 Aug;297(2):E304-14
references.pmid: 19491292
references.citation: J Clin Invest. 1995 Aug;96(2):1137-44
references.pmid: 7635950
references.citation: Nat Cell Biol. 2010 Feb;12(2):143-52
references.pmid: 20081842
references.citation: Exp Physiol. 2007 Jan;92(1):207-17
references.pmid: 16945942
references.citation: Front Biosci (Landmark Ed). 2009 Jan 01;14:19-44
references.pmid: 19273052
references.citation: J Appl Physiol (1985). 2004 Feb;96(2):575-83
references.pmid: 14555687
references.citation: J Cell Biol. 1994 Jun;125(6):1275-87
references.pmid: 8207057
references.citation: Am J Physiol Cell Physiol. 2013 Oct 15;305(8):C887-95
references.pmid: 23926128
references.citation: Science. 2005 Jan 21;307(5708):384-7
references.pmid: 15662004
references.citation: J Anim Sci. 1979 Jul;49(1):115-27
references.pmid: 500507
references.citation: Am J Physiol Endocrinol Metab. 2004 Aug;287(2):E310-7
references.pmid: 15068958
references.citation: Am J Physiol Endocrinol Metab. 2010 Apr;298(4):E751-60
references.pmid: 20103737
references.citation: Med Sci Sports Exerc. 2004 Jan;36(1):28-34
references.pmid: 14707764
references.citation: J Endocrinol. 2000 Dec;167(3):429-37
references.pmid: 11115769
references.citation: Development. 2007 Dec;134(23):4131-40
references.pmid: 17959722
references.citation: J Mol Med (Berl). 2008 Oct;86(10):1113-26
references.pmid: 18574572
references.citation: Nat Commun. 2011 Oct 11;2:499
references.pmid: 21988915
references.citation: Eur J Nutr. 2009 Feb;48(1):62-5
references.pmid: 19099241
references.citation: J Clin Invest. 2012 May;122(5):1764-76
references.pmid: 22505452
references.citation: J Vis Exp. 2009 Sep 21;(31):
references.pmid: 19770816
references.citation: FEBS Lett. 1999 Oct 29;460(2):343-8
references.pmid: 10544261
references.citation: Cancer Prev Res (Phila). 2011 Mar;4(3):329-46
references.pmid: 21372033
references.citation: Can J Appl Physiol. 2001 Feb;26(1):102-22
references.pmid: 11173672
references.citation: Cell Metab. 2006 Dec;4(6):465-74
references.pmid: 17141630
references.citation: J Biol Chem. 2004 Jan 9;279(2):1070-9
references.pmid: 14573616
references.citation: J Clin Invest. 2003 Jan;111(1):91-8
references.pmid: 12511592
references.citation: J Endocrinol. 2012 Mar;212(3):277-90
references.pmid: 21903861
references.citation: J Biol Chem. 2010 Jun 18;285(25):19051-9
references.pmid: 20421294
references.citation: Cancer Res. 2009 Jul 1;69(13):5392-9
references.pmid: 19509226
references.citation: Nutr Metab (Lond). 2006 Aug 10;3:31
references.pmid: 16901342
references.citation: J Anat. 1987 Feb;150:129-43
references.pmid: 3654328