Leucine-rich diet supplementation modulates foetal muscle protein metabolism impaired by Walker-256 tumour

Author(s)

Cruz, Bread ^[1] ; Gomes-Marcondes, Maria C. C. ^[1]

Affiliation

^[1] State Univ Campinas UNICAMP, Lab Nutr & Canc, Dept Struct & Funct Biol, Inst Biol, BR-13083862 Sao Paulo - Brazil

• Document type: Journal article
• Source: Reproductive Biology and Endocrinology; v. 12, JAN 3 2014.
• Web of Science Citations: 12

Abstract

Background: Cancer-cachexia induces a variety of metabolic disorders of protein turnover and is more pronounced when associated with pregnancy. Tumour-bearing pregnant rats have impaired protein balance, which decreases protein synthesis and increases muscle breakdown. Because branched-chain amino acids, especially leucine, stimulate protein synthesis, we investigated the effect of a leucine-rich diet on protein metabolism in the foetal gastrocnemius muscles of tumour-bearing pregnant rats. Methods: Foetuses of pregnant rats with or without Walker 256 tumours were divided into six groups. During the 20 days of the experiment, the pregnant groups were fed with either a control diet (C, control rats; W, tumour-bearing rats; Cp, rats pair-fed the same normoprotein-diet as the W group) or with a leucine-rich diet (L, leucine rats; LW, leucine tumour-bearing rats; and Lp, rats pair-fed the same leucine-rich diet as the LW group). After the mothers were sacrificed, the foetal gastrocnemius muscle samples were resected, and the protein synthesis and degradation and tissue chymotrypsin-like, cathepsin and calpain enzyme activities were assayed. The muscle oxidative enzymes (catalase, glutathione-S-transferase and superoxide dismutase), alkaline phosphatase enzyme activities and lipid peroxidation (malondialdehyde) were also measured. Results: Tumour growth led to a reduction in foetal weight associated with decreased serum protein, albumin and glucose levels and low haematocrit in the foetuses of the W group, whereas in the LW foetuses, these changes were less pronounced. Muscle protein synthesis (measured by L-{[}3H]-phenylalanine incorporation) was reduced in the W foetuses but was restored in the LW group. Protein breakdown (as assessed by tyrosine release) was enhanced in the L and W groups, but chymotrypsin-like activity increased only in group W and tended toward an increase in the LW foetuses. The activity of cathepsin H was significantly higher in the W group foetuses, but the proteolytic calcium-dependent pathway showed similar enzyme activity. In parallel, an intense oxidative stress process was observed only in the group W foetuses. Conclusions: These data suggested that the proteasomal and lysosomal proteolytic pathways and oxidative stress are likely to participate in the process of foetal muscle catabolism of Walker's tumour-bearing pregnant rats. The present work shows that foetal muscle can be protected by supplementation with a leucine-rich diet. (AU)

• FAPESP's process: 11/08276-0 - Modultation of L-leucine on cell signaling and metabolic pathways of muscle protein metabolism in Walker 256 tumor-bearing rats.
• Grantee: Bread Leandro Gomes da Cruz
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 10/00209-9 - Nutritional supplementation and cancer cachexia. Biochemical and molecular studies
• Grantee: Maria Cristina Cintra Gomes Marcondes
• Support Opportunities: Regular Research Grants