title: Identification and validation of novel contraction-regulated myokines released from primary human skeletal muscle cells.
abstract: Proteins secreted by skeletal muscle, so called myokines, have been shown to affect muscle physiology and additionally exert systemic effects on other tissues and organs. Although recent profiling studies have identified numerous myokines, the amount of overlap from these studies indicates that the secretome of skeletal muscle is still incompletely characterized. One limitation of the models used is the lack of contraction, a central characteristic of muscle cells. Here we aimed to characterize the secretome of primary human myotubes by cytokine antibody arrays and to identify myokines regulated by contraction, which was induced by electrical pulse stimulation (EPS). In this study, we validated the regulation and release of two selected myokines, namely pigment epithelium derived factor (PEDF) and dipeptidyl peptidase 4 (DPP4), which were recently described as adipokines. This study reveals that both factors, DPP4 and PEDF, are secreted by primary human myotubes. PEDF is a contraction-regulated myokine, although PEDF serum levels from healthy young men decrease after 60 min cycling at VO2max of 70%. Most interestingly, we identified 52 novel myokines which have not been described before to be secreted by skeletal muscle cells. For 48 myokines we show that their release is regulated by contractile activity. This profiling study of the human skeletal muscle secretome expands the number of myokines, identifies novel contraction-regulated myokines and underlines the overlap between proteins which are adipokines as well as myokines.
authors: Paul-Langerhans-Group of Integrative Physiology, German Diabetes Center, Düsseldorf, Germany.
authors: Silja
authors: S
authors: Raschke
authors: Kristin
authors: K
authors: Eckardt
authors: Kirsten
authors: K
authors: Bjørklund Holven
authors: Jørgen
authors: J
authors: Jensen
authors: Jürgen
authors: J
authors: Eckel
mesh_terms: D054392:Adipokines / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D018819:Dipeptidyl Peptidase 4 / Q000097:blood / Q000378:metabolism; D005136:Eye Proteins / Q000097:blood / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D032342:Muscle Cells / Q000378:metabolism*; D009119:Muscle Contraction / Q000502:physiology*; D009124:Muscle Proteins / Q000097:blood / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000097:blood / Q000378:metabolism; D040081:Protein Array Analysis; D015843:Serpins / Q000097:blood / Q000378:metabolism; D055815:Young Adult; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D054392:Adipokines; D018819:Dipeptidyl Peptidase 4; D005136:Eye Proteins; D009124:Muscle Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor
references: FASEB J. 2004 Jun;18(9):992-4
references: 15059966
references: Nature. 2012 Jan 11;481(7382):463-8
references: 22237023
references: Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6874-9
references: 10823914
references: Am J Physiol Heart Circ Physiol. 2010 Sep;299(3):H857-62
references: 20543089
references: Arthritis Rheum. 2010 Jul;62(7):2144-51
references: 20309865
references: Mol Cell Proteomics. 2011 May;10(5):M110.004804
references: 21343469
references: J Biol Chem. 2003 Nov 14;278(46):45777-84
references: 12952969
references: Proteomics. 2009 Jan;9(1):51-60
references: 19053084
references: Drugs. 2011 Jul 30;71(11):1441-67
references: 21812507
references: Am J Physiol Heart Circ Physiol. 2009 Mar;296(3):H735-44
references: 19151248
references: Arch Physiol Biochem. 2006 Apr;112(2):105-13
references: 16931452
references: Skelet Muscle. 2011 Feb 01;1(1):6
references: 21798084
references: Diabetes. 2011 Jul;60(7):1917-25
references: 21593202
references: PLoS One. 2012;7(11):e51066
references: 23226462
references: Lymphat Res Biol. 2006;4(2):73-82
references: 16808669
references: Genome Biol. 2009;10(11):R130
references: 19919682
references: Cancer Lett. 2002 Jan 25;175(2):181-5
references: 11741746
references: Diabetologia. 1998 Mar;41(3):300-6
references: 9541170
references: Cancer Immunol Immunother. 2009 Nov;58(11):1723-47
references: 19557413
references: Diabetologia. 2012 Apr;55(4):1128-39
references: 22282161
references: Am J Physiol Cell Physiol. 2010 Apr;298(4):C807-16
references: 20089933
references: Sports Med. 2001;31(15):1063-82
references: 11735686
references: J Proteome Res. 2007 Feb;6(2):698-710
references: 17269726
references: J Anim Sci. 2012 Apr;90(4):1126-33
references: 22100600
references: Int J Obes (Lond). 2008 Jul;32(7):1113-21
references: 18414424
references: Arterioscler Thromb Vasc Biol. 2009 Jun;29(6):969-74
references: 19342599
references: Cell. 2003 May 16;113(4):483-94
references: 12757709
references: Int J Biochem Cell Biol. 2008;40(10):2303-14
references: 18490187
references: J Physiol. 2012 Feb 1;590(3):595-606
references: 22155930
references: J Physiol. 1999 Feb 15;515 ( Pt 1):287-91
references: 9925898
references: J Biol Chem. 2012 Apr 6;287(15):11968-80
references: 22351773
references: Exerc Immunol Rev. 2006;12:6-33
references: 17201070
references: Diabetes. 2002 Dec;51(12):3391-9
references: 12453891
references: Eur J Immunol. 1996 Mar;26(3):640-7
references: 8605932
references: Diabetes. 2006 Oct;55(10):2688-97
references: 17003332
references: Histochem Cell Biol. 2007 Jan;127(1):31-40
references: 16924525
references: Proc Natl Acad Sci U S A. 2006 May 9;103(19):7315-20
references: 16670201
references: J Neuroimmunol. 2003 Apr;137(1-2):125-33
references: 12667656
references: Diabetes. 2009 Mar;58(3):579-89
references: 19074989
references: Clin Endocrinol (Oxf). 2011 Oct;75(4):464-9
references: 21521346
references: Mol Cell Proteomics. 2012 Jan;11(1):M111.010504
references: 21947364
references: Proteins. 2006 Mar 15;62(3):776-92
references: 16342272
references: J Clin Endocrinol Metab. 2006 Jun;91(6):2447-50
references: 16522692
references: J Clin Endocrinol Metab. 2005 Apr;90(4):2282-9
references: 15671098
references: Am J Physiol Endocrinol Metab. 2011 Sep;301(3):E504-10
references: 21653222
references: Int J Obes (Lond). 2005 Jan;29(1):146-50
references: 15520826
references: Eur J Biochem. 1993 Jun 15;214(3):829-35
references: 8100523
references: Inflammation. 2013 Feb;36(1):226-31
references: 22961567
references: Diabetes. 2002 Aug;51(8):2369-76
references: 12145147
references: Science. 1995 Jun 9;268(5216):1495-9
references: 7770776
references: Trends Endocrinol Metab. 2011 May;22(5):171-8
references: 21420315
references: Am J Physiol Endocrinol Metab. 2011 Nov;301(5):E1013-21
references: 21828336
references: Clin Exp Immunol. 1998 Sep;113(3):407-14
references: 9737670
references: Diabetes Res Clin Pract. 2008 Oct;82(1):e5-7
references: 18715664
references: J Proteome Res. 2011 Dec 2;10(12):5315-25
references: 22023146
references: J Endocrinol. 2000 Dec;167(3):403-15
references: 11115767
references: J Appl Physiol (1985). 2011 Jul;111(1):251-9
references: 21527666
references: Am J Physiol. 1996 Sep;271(3 Pt 1):E601-5
references: 8843757
references: Med Sci Sports Exerc. 2010 Nov;42(11):2023-9
references: 20386333
references: J Cell Biol. 1992 Mar;116(5):1071-80
references: 1740466
references: Am J Physiol Cell Physiol. 2008 May;294(5):C1183-91
references: 18353892
references: Diabetes. 2009 Jan;58(1):30-8
references: 18835929
references: J Appl Physiol (1985). 2009 Jan;106(1):130-7
references: 18974369
references: Neuromuscul Disord. 2003 Mar;13(3):223-35
references: 12609504
references: Eur J Heart Fail. 2008 Nov;10(11):1065-72
references: 18805052
references: Immunol Lett. 1994 Oct;42(3):135-8
references: 7890313
references: Mol Cell Proteomics. 2010 Nov;9(11):2482-96
references: 20631206
references: Proc Natl Acad Sci U S A. 1986 Sep;83(18):6844-8
references: 3462731
references: Acta Diabetol. 2012 Dec;49 Suppl 1:S161-9
references: 22547263
references: Proc Natl Acad Sci U S A. 1993 Feb 15;90(4):1526-30
references: 8434014
references: Cell Metab. 2012 Mar 7;15(3):405-11
references: 22405075
references: Endocr Rev. 2009 Apr;30(2):152-77
references: 19240267
references: J Bone Miner Res. 2010 May;25(5):1128-37
references: 20200998
references: Brain Res. 2011 May 16;1390:1-9
references: 21420941
references: J Appl Physiol Respir Environ Exerc Physiol. 1984 Apr;56(4):831-8
references: 6373687
references: Exp Eye Res. 1991 Sep;53(3):411-4
references: 1936177
references: J Appl Physiol (1985). 2005 Apr;98(4):1154-62
references: 15772055
references: Angiogenesis. 2004;7(3):255-67
references: 15609080
references: Diabetes. 2007 Sep;56(9):2185-93
references: 17563068
references: Adv Exp Med Biol. 1997;425:223-37
references: 9433504
references: Int J Obes (Lond). 2011 Jun;35(6):762-72
references: 20938440
references: J Cell Biochem. 2005 Sep 1;96(1):89-96
references: 16052473
references: J Proteome Res. 2011 Oct 7;10(10):4769-88
references: 21823675
references: J Exp Biol. 2011 Jan 15;214(Pt 2):337-46
references: 21177953
references: Adv Immunol. 1994;55:97-179
references: 8304236
references: Curr Opin Lipidol. 2007 Jun;18(3):258-62
references: 17495598
references: Diabetes. 2009 Dec;58(12):2731-40
references: 19720798
references: J Clin Endocrinol Metab. 2003 Jul;88(7):3005-10
references: 12843134
references: PLoS One. 2012;7(3):e33203
references: 22457744
references: Am J Physiol Regul Integr Comp Physiol. 2008 May;294(5):R1628-37
references: 18353886
references: J Physiol. 2008 Apr 15;586(8):2195-201
references: 18292129
references: Am J Physiol Endocrinol Metab. 2002 Dec;283(6):E1272-8
references: 12388119
references: Int J Obes Relat Metab Disord. 2004 Aug;28(8):985-92
references: 15211372
references: Trends Pharmacol Sci. 2007 Apr;28(4):152-6
references: 17331593
references: J Physiol. 2007 Oct 1;584(Pt 1):305-12
references: 17690139
references: Exp Biol Med (Maywood). 2008 Sep;233(9):1171-80
references: 18535166
references: Endocrinology. 2002 Feb;143(2):492-503
references: 11796503
references: Int Immunol. 2000 Sep;12(9):1329-35
references: 10967028
references: J Clin Endocrinol Metab. 2010 Oct;95(10):4720-8
references: 20631025
references: J Endocrinol. 2005 Sep;186(3):457-65
references: 16135665
references: Transl Res. 2012 Feb;159(2):118-24
references: 22243796
references: Diabetologia. 2009 Jul;52(7):1409-18
references: 19387610
references: J Physiol Biochem. 2011 Mar;67(1):87-94
references: 20936392
references: Indian J Endocrinol Metab. 2012 Jan;16(1):116-23
references: 22276262