Roeseler de Rivera, Francois-Xavier P.G. (2011) The effects of LPS plus pro-inflammatory cytokines on glycogen synthesis in C2C12 myocytes. Doctoral thesis (DPhil), University of Sussex.

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Abstract

Culturing C2C12 myoblasts and myotubes with a combination of LPS, TNF-α, IFN-γ and IL1β for 18 hours was used to determine the effects of endotoxic shock on possible causes of the dysregulation of glucose homeostasis associated with the syndrome. The in vitro model was confirmed by the significant production of NO in both myoblasts and myotubes following treatment. The treatment resulted in significantly different results between both myocyte preparations with regards to the regulation of glycogen synthesis.

In the myoblasts, the treatment significantly increased myoblast glycogen synthesis, in a NO-independent manner, as seen by the inclusion of the NO synthase inhibitor L-NAME. This stimulation was unlikely to be due to a change in either GS or Phosphorylase activity. However it may have been caused by a significant increase in glucose transport induced by the treatment. This latter increase was also NO-independent, as well as not requiring reactive oxygen species. Insulin-induced myoblast protein synthesis was impaired by the treatment, which is likely due to an impairment of insulin-stimulated ERK1/2 phosphorylation.

In the myotubes the case was different, as the treatment significantly reduced glycogen synthesis in a NO-dependent manner. This correlated with a NO-dependent increase in GS phosphorylation, indicating it was less active, however measurements of GS fractional activity failed to confirm this. Insulin stimulation of myotube glycogen synthesis was impaired by the treatment in a NO-independent manner, which may have involved an impairment of the insulin signal to ERK1/2. However the latter impairment was NO-dependent, suggesting other contributory mechanisms.

Endotoxic treatment significantly increased myoblast protein content, but failed to do so in myotubes. This effect in the myoblasts may be explained by a significant increase in protein synthesis between 6 and 12 hours of treatment. None of the effects observed in the study were due to the treatment compromising cell viability.

Item Type:	Thesis (Doctoral)
Schools and Departments:	School of Life Sciences > Biochemistry
Subjects:	Q Science > QD Chemistry > QD0241 Organic chemistry > QD0415 Biochemistry Q Science > QH Natural history > QH0301 Biology > QH0573 Cytology
Depositing User:	Library Cataloguing
Date Deposited:	01 Mar 2011 12:27
Last Modified:	13 Aug 2015 14:44
URI:	http://sro.sussex.ac.uk/id/eprint/6321

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