Oita, Radu Cristian
(2011).
The role of extracellular form of visfatin (eNAMPT) in modulating stress responses in cultured myocytes as a model of skeletal muscle ageing.
University of Birmingham.
Ph.D.
Abstract
The understanding of the ageing process and of ageing-associated diseases represents a significant challenge for the scientific community, governments and society at large. I identified in skeletal muscle of murine models by microarray an increase in PPAR-β/δ expression during acute phase of hindlimb suspension (accelerated ageing), with a possible compensatory role, and an increase in expression levels of NR4A family of nuclear receptors in the skeletal muscle of caloric restricted rats (decelerated ageing). Adipose tissue has an endocrine role being actively involved in cross-talk with peripheral organs such as skeletal muscle. Visfatin is a recently discovered adipokine with pleiotropic functions. Unlike in other types of cells, in differentiated C2C12 myoblasts exogenous added visfatin (eNampt) did not act as an insulin-mimetic factor as shown by western blot and fluorescent assays. Visfatin treatment of differentiated C2C12 myotubes generated nevertheless an increase in the levels of reactive oxygen species as shown by fluorescent microscopy that was dependent on de novo transcription and translation of a new set of genes as revealed by RT-PCR. This increase in oxidative stress was independent of activation of the stress-activated protein kinases (MAPKs) such as ERK and p38, but dependent on NFkB activation as proved by western blot.
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