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Article
Muscle glycogen synthase isoform is responsible for testicular glycogen synthesis: Glycogen overproduction induces apoptosis in male germ cells
Article first published online: 9 MAY 2013
DOI: 10.1002/jcb.24507
Copyright © 2013 Wiley Periodicals, Inc.
Additional Information
How to Cite
Villarroel-Espíndola, F., Maldonado, R., Mancilla, H., vander Stelt, K., Acuña, A. I., Covarrubias, A., López, C., Angulo, C., Castro, M. A., Carlos Slebe, J., Durán, J., García-Rocha, M., Guinovart, J. J. and Concha, I. I. (2013), Muscle glycogen synthase isoform is responsible for testicular glycogen synthesis: Glycogen overproduction induces apoptosis in male germ cells. J. Cell. Biochem., 114: 1653–1664. doi: 10.1002/jcb.24507
Publication History
- Issue published online: 9 MAY 2013
- Article first published online: 9 MAY 2013
- Accepted manuscript online: 5 FEB 2013 08:17AM EST
- Manuscript Accepted: 22 JAN 2013
- Manuscript Received: 18 NOV 2012
Funded by
- FONDECYT (Fondo Nacional de Desarrollo Científico y Tecnológico). Grant Numbers: 1110508, 1090740, 1110571
- DID-UACh (Dirección de Investigación y Desarrollo, Universidad Austral de Chile)
- Ministerio de Economía y Competitividad. Grant Number: BFU2011-30554
- Generalitat de Catalunya. Grant Number: 2009 SGR 01176
- CIBER de Diabetes y Enfermedades Metabólicas Asociadas (ISCIII, Ministerio de Economía y Competitividad). Grant Number: S-201-14
- Dirección de Estudios Postgrados and Escuela de Graduados, Facultad de Ciencias, Universidad Austral de Chile
- CONICYT (Comisión Nacional de Investigación Científica y Tecnológica). Grant Number: AT24100011
- MECESUP (Programa de Mejoramiento de la Calidad y Equidad de la Educación Superior). Grant Numbers: UCO0606, AUS0704
Keywords:
- GLYCOGEN SYNTHASE;
- GLYCOGEN;
- TESTIS;
- SEMINIFEROUS TUBULES;
- APOPTOSIS
Abstract
Glycogen is the main source of glucose for many biological events. However, this molecule may have other functions, including those that have deleterious effects on cells. The rate-limiting enzyme in glycogen synthesis is glycogen synthase (GS). It is encoded by two genes, GYS1, expressed in muscle (muscle glycogen synthase, MGS) and other tissues, and GYS2, primarily expressed in liver (liver glycogen synthase, LGS). Expression of GS and its activity have been widely studied in many tissues. To date, it is not clear which GS isoform is responsible for glycogen synthesis and the role of glycogen in testis. Using RT-PCR, Western blot and immunofluorescence, we have detected expression of MGS but not LGS in mice testis during development. We have also evaluated GS activity and glycogen storage at different days after birth and we show that both GS activity and levels of glycogen are higher during the first days of development. Using RT-PCR, we have also shown that malin and laforin are expressed in testis, key enzymes for regulation of GS activity. These proteins form an active complex that regulates MGS by poly-ubiquitination in both Sertoli cell and male germ cell lines. In addition, PTG overexpression in male germ cell line triggered apoptosis by caspase3 activation, proposing a proapoptotic role of glycogen in testis. These findings suggest that GS activity and glycogen synthesis in testis could be regulated and a disruption of this process may be responsible for the apoptosis and degeneration of seminiferous tubules and possible cause of infertility. J. Cell. Biochem. 114: 1653–1664, 2013. © 2013 Wiley Periodicals, Inc.