title: TNF-alpha acts via p38 MAPK to stimulate expression of the ubiquitin ligase atrogin1/MAFbx in skeletal muscle.
abstract: Atrogin1/MAFbx is an ubiquitin ligase that mediates muscle atrophy in a variety of catabolic states. We recently found that H2O2 stimulates atrogin1/MAFbx gene expression. Since the cytokine tumor necrosis factor-alpha (TNF-alpha) stimulates both reactive oxygen production and general activity of the ubiquitin conjugating pathway, we hypothesized that TNF-alpha would also increase atrogin1/MAFbx gene expression. As with H2O2, we found that TNF-alpha exposure up-regulates atrogin1/MAFbx mRNA within 2 h in C2C12 myotubes. Intraperitoneal injection of TNF-alpha increased atrogin1/MAFbx mRNA in skeletal muscle of adult mice within 4 h. Exposing myotubes to either TNF-alpha or H2O2 also produced general activation of the mitogen-activated protein kinases (MAPKs): p38, ERK1/2, and JNK. The increase in atrogin1/MAFbx gene expression induced by TNF-alpha was not altered significantly by ERK inhibitor PD98059 or the JNK inhibitor SP600125. In contrast, atrogin1/MAFbx up-regulation and the associated increase in ubiquitin conjugating activity were both blunted by p38 inhibitors, either SB203580 or curcumin. These data suggest that TNF-alpha acts via p38 to increase atrogin1/MAFbx gene expression in skeletal muscle.
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA. yiping@bcm.tmc.edu
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Li
authors.forename: Yuling
authors.initials: Y
authors.lastname: Chen
authors.forename: Joseph
authors.initials: J
authors.lastname: John
authors.forename: Jennifer
authors.initials: J
authors.lastname: Moylan
authors.forename: Bingwen
authors.initials: B
authors.lastname: Jin
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Mann
authors.forename: Michael B
authors.initials: MB
authors.lastname: Reid
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000201:enzymology; D009124:Muscle Proteins / Q000235:genetics*; D018482:Muscle, Skeletal / Q000201:enzymology*; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D009124:Muscle Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D006861:Hydrogen Peroxide; C486691:Fbxo32 protein, mouse; D044843:SKP Cullin F-Box Protein Ligases; D048051:p38 Mitogen-Activated Protein Kinases
references.citation: Surg Infect (Larchmt). 2003 Spring;4(1):17-27
references.pmid: 12744763
references.citation: FASEB J. 2003 Jun;17(9):1048-57
references.pmid: 12773487
references.citation: FEBS Lett. 2003 Jun 5;544(1-3):214-7
references.pmid: 12782319
references.citation: Am J Physiol Cell Physiol. 2003 Aug;285(2):C391-8
references.pmid: 12711594
references.citation: Am J Physiol Cell Physiol. 2003 Oct;285(4):C806-12
references.pmid: 12773310
references.citation: Diabetologia. 2003 Oct;46(10):1324-8
references.pmid: 12937895
references.citation: FASEB J. 2004 Jan;18(1):39-51
references.pmid: 14718385
references.citation: Ann Neurol. 2004 Feb;55(2):195-206
references.pmid: 14755723
references.citation: Cell. 2004 Apr 30;117(3):399-412
references.pmid: 15109499
references.citation: Mol Cell. 2004 May 7;14(3):395-403
references.pmid: 15125842
references.citation: Am J Physiol Endocrinol Metab. 2004 Oct;287(4):E591-601
references.pmid: 15100091
references.citation: Nature. 1970 Aug 15;227(5259):680-5
references.pmid: 5432063
references.citation: Biotechniques. 1990 Nov;9(5):558, 560
references.pmid: 1702642
references.citation: Biochemistry. 1991 Jul 30;30(30):7514-22
references.pmid: 1649632
references.citation: Genes Dev. 1992 Aug;6(8):1444-56
references.pmid: 1379563
references.citation: Br J Cancer. 1993 Jan;67(1):15-23
references.pmid: 8427775
references.citation: FEBS Lett. 1993 Jun 1;323(3):211-4
references.pmid: 8388807
references.citation: Mol Cell Biochem. 1993 Aug 11;125(1):11-8
references.pmid: 8264567
references.citation: Life Sci. 1994;55(18):1383-91
references.pmid: 7934649
references.citation: FEBS Lett. 1995 May 8;364(2):229-33
references.pmid: 7750577
references.citation: Proc Natl Acad Sci U S A. 1995 Aug 29;92(18):8115-9
references.pmid: 7667254
references.citation: J Biol Chem. 1995 Nov 17;270(46):27489-94
references.pmid: 7499206
references.citation: EMBO J. 1996 Apr 15;15(8):1753-65
references.pmid: 8617220
references.citation: Biochem Biophys Res Commun. 1997 Jan 13;230(2):238-41
references.pmid: 9016756
references.citation: FASEB J. 1998 Jul;12(10):871-80
references.pmid: 9657527
references.citation: Annu Rev Biochem. 1998;67:425-79
references.pmid: 9759494
references.citation: Curr Opin Cardiol. 1999 May;14(3):211-6
references.pmid: 10358792
references.citation: J Clin Invest. 1999 Nov;104(10):1411-20
references.pmid: 10562303
references.citation: Proc Soc Exp Biol Med. 1999 Dec;222(3):253-62
references.pmid: 10601884
references.citation: Crit Care Med. 2000 Apr;28(4 Suppl):N67-77
references.pmid: 10807318
references.citation: Ann N Y Acad Sci. 2000 Jun;908:341-3
references.pmid: 10911981
references.citation: Circulation. 2000 Oct 3;102(14):1690-6
references.pmid: 11015349
references.citation: Science. 2000 Sep 29;289(5488):2293-4
references.pmid: 11041796
references.citation: Acta Physiol Scand. 2001 Mar;171(3):225-32
references.pmid: 11412134
references.citation: Curr Opin Clin Nutr Metab Care. 2001 May;4(3):183-90
references.pmid: 11517350
references.citation: Curr Opin Rheumatol. 2001 Nov;13(6):483-7
references.pmid: 11698724
references.citation: Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):13681-6
references.pmid: 11717429
references.citation: Science. 2001 Nov 23;294(5547):1704-8
references.pmid: 11679633
references.citation: Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14440-5
references.pmid: 11717410
references.citation: IUBMB Life. 2001 Jul;52(1-2):3-6
references.pmid: 11795590
references.citation: Sci STKE. 2002 Apr 30;2002(130):pe21
references.pmid: 11983938
references.citation: Dev Biol. 2002 Oct 1;250(1):1-23
references.pmid: 12297093
references.citation: Mol Immunol. 2002 Dec;39(9):509-17
references.pmid: 12431383
references.citation: J Physiol. 2003 Mar 15;547(Pt 3):977-87
references.pmid: 12562918
references.citation: Int J Biochem Cell Biol. 2003 May;35(5):698-705
references.pmid: 12672461