Leucine modulates the effect of Walker factor, a proteolysis-inducing factor-like protein from Walker tumours, on gene expression and cellular activity in C2C12 myotubes

Author(s)

Goncalves, Estela Maria ^[1] ; Salomao, Emilianne Miguel ^[1] ; Cintra Gomes-Marcondes, Maria Cristina ^[1]

Affiliation

^[1] State Univ Campinas UNICAMP, Inst Biol, Dept Struct & Funct Biol, BR-13083970 Campinas, SP - Brazil

• Document type: Journal article
• Source: CYTOKINE; v. 64, n. 1, p. 343-350, OCT 2013.
• Web of Science Citations: 7

Abstract

Cancer-cachexia causes severe weight loss, particularly from the wasting of skeletal muscle, which occurs due to increased protein catabolism and/or decreased protein synthesis. The muscle protein degradation observed in cancer patients is mediated by a specific cytokine, proteolysis-inducing factor (PIF), which is produced by the tumour. This protein increases the ubiquitin-proteasome pathway activity, and the synthesis of muscle protein in these patients can be affected by several factors, including nutrient-related signalling. Some nutrients, such as leucine, can decrease the ubiquitin-proteasome pathway activity and increase the skeletal muscle protein content in cachectic animals. In this study, we investigated the effects of leucine on cell viability, morphology, functional proteasome activity, enzymatic activity, and protein synthesis and degradation in C2C12 myotubes exposed to the proteolysis-inducing factor (PIF)-like protein purified from Walker tumour-bearing rats. Walker factor (WF) had no cytotoxic effects on myotube cells and morphological characteristics were not altered in the presence of WF and/or leucine. However, increased alkaline phosphatase activity was observed. At higher WE concentrations, chymotrypsin-like activity, cathepsin B activity and 20S proteasome gene expression increased. Treating myotubes with leucine before exposure to WF causes leads to a decrease in proteasome activity as well as the activity of chymotrypsin and cathepsin enzymes. Total protein synthesis decreased in WF-treated cells concomitantly as protein degradation increased. After leucine exposure, the observed effects of WF were minimal or even reverted in some cases. Taken together, these results suggest an important modulatory effect for leucine on the effects of WF in C2C12 myotube cells. (C) 2013 Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 10/11328-9 - Muscle protein synthesis and degradation in tumour-bearing rats under nutritional supplementation and exercise
• Grantee: Maria Cristina Cintra Gomes Marcondes
• Support Opportunities: Regular Research Grants
• FAPESP's process: 10/00260-4 - Control of translation of protein synthesis in skeletal muscle model of Cancer cachexia-under the effects of physical activity associated with nutritional supplementation of leucine
• Grantee: Emilianne Miguel Salomão
• Support Opportunities: Scholarships in Brazil - Post-Doctoral