title: Gravitational force modulates G2/M phase exit in mechanically unloaded myoblasts.
abstract: Prolonged spaceflight gives rise to muscle loss and reduced strength, a condition commonly referred to as space atrophy. During exposure to microgravity, skeletal muscle myoblasts are mechanically unloaded and respond with attenuated cell proliferation, slowed cell cycle progression, and modified protein expression. To elucidate the underlying mechanisms by which muscle mass declines in response to prolonged microgravity exposure, we grew C2C12 mouse muscle cells under conditions of simulated microgravity (SM) and analyzed their proliferative capacity, cell cycle progression, and cyclin B and D expression. We demonstrated that the retarded cell growth observed in SM was correlated with an approximate 16 h delay in G2/M phase progression, where cells accumulated specifically between the G2 checkpoint and the onset of anaphase, concomitantly with a positive expression for cyclin B. The effect was specific for gravitational mechanical unloading as cells grown under conditions of hypergravity (HG, 4 g) for similar durations of time exhibited normal proliferation and normal cell cycle progression. Our results show that SM and HG exert phenomenological distinct responses over cell cycle progression. The deficits of SM can be restored by terrestrial gravitational force, whereas the effects of HG are indistinguishable from the 1 g control. This suggests that the mechanotransduction apparatus of cells responds differently to mechanical unloading and loading.
authors: CC Aerospace Biomedical Science & Technology; Space Biology Group; University of Applied Sciences and Arts; Hergiswil, Switzerland; Institute for Biomechanics; Eidgenössische Technische Hochschule Zürich; Zürich, Switzerland.
authors: Tatiana
authors: T
authors: Benavides Damm
authors: Alfredo
authors: A
authors: Franco-Obregón
authors: Marcel
authors: M
authors: Egli
mesh_terms: D000705:Anaphase; D000818:Animals; D002455:Cell Division; D002460:Cell Line; D049109:Cell Proliferation; D019926:Cyclin B / Q000378:metabolism; D056741:Cyclin D / Q000378:metabolism; D016195:G2 Phase; D018471:Hypergravity; D040542:Mechanotransduction, Cellular; D051379:Mice; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism; D013997:Time Factors; D018474:Weightlessness Simulation
chemical_list: D019926:Cyclin B; D056741:Cyclin D
keywords: cell cycle; cyclins; hypergravity; mechanical unloading; mechanotransduction; microgravity; muscle atrophy
references: J Neurol Sci. 1988 Apr;84(2-3):275-94
references: 3379447
references: Eur J Appl Physiol. 2011 Mar;111(3):403-20
references: 20617334
references: J Musculoskelet Neuronal Interact. 2000 Dec;1(2):157-60
references: 15758512
references: J Cell Biol. 1990 Jul;111(1):183-96
references: 2114410
references: FASEB J. 1999 Jun;13(9):1031-8
references: 10336885
references: J Biosci Bioeng. 2012 Feb;113(2):258-61
references: 22055920
references: Biol Reprod. 2003 Nov;69(5):1552-64
references: 12826587
references: Cell Biol Int. 1999;23(6):407-15
references: 10623420
references: FASEB J. 2001 Apr;15(6):1104-6
references: 11292682
references: Eur J Cell Biol. 2012 Nov-Dec;91(11-12):834-46
references: 22727433
references: J Cell Biol. 1991 Oct;115(1):1-17
references: 1717476
references: Cell Mol Life Sci. 2005 Nov;62(21):2405-13
references: 16003492
references: FASEB J. 2013 May;27(5):2045-54
references: 23363573
references: Gerontology. 2010;56(2):157-66
references: 19851058
references: Physiology (Bethesda). 2010 Feb;25(1):50-6
references: 20134028
references: Curr Cancer Drug Targets. 2013 Jan;13(1):103-16
references: 22920441
references: Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8364-8
references: 10880562
references: EMBO J. 1989 Jan;8(1):73-82
references: 2469574
references: Respir Res. 2009 Dec 11;10:123
references: 20003325
references: Nature. 1993 Nov 18;366(6452):211-2
references: 8232578
references: Cancer Lett. 2009 Sep 28;283(1):43-51
references: 19394138
references: FASEB J. 1998 Aug;12(11):1007-18
references: 9707173
references: Am J Respir Cell Mol Biol. 2010 Jul;43(1):26-34
references: 19648475
references: Cancer Res. 2009 Aug 15;69(16):6565-72
references: 19638577
references: J Exp Biol. 2001 Sep;204(Pt 18):3201-8
references: 11581335
references: Cell Physiol Biochem. 2013;31(2-3):432-51
references: 23548630
references: J Biol Chem. 2003 Sep 5;278(36):33730-7
references: 12821654
references: Curr Biol. 2003 Mar 4;13(5):373-83
references: 12620185
references: Cytometry. 1996 Sep 1;25(1):1-13
references: 8875049
references: Biochem Biophys Res Commun. 1998 Mar 17;244(2):317-24
references: 9514855
references: Cytometry. 1987 Jan;8(1):1-8
references: 3803091
references: J Physiol. 2006 Sep 15;575(Pt 3):913-24
references: 16825296
references: Cell Signal. 2003 Nov;15(11):1049-57
references: 14499348
references: PLoS One. 2006 Dec 27;1:e128
references: 17205132