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Evaluation of leucine supplementation on the tumor factors effects in H9c2 cardiac cells

Grant number: 20/13222-5
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): August 01, 2021
Status:Discontinued
Field of knowledge:Biological Sciences - Physiology - General Physiology
Principal Investigator:Maria Cristina Cintra Gomes Marcondes
Grantee:Maiara Caroline Colombera
Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:17/02739-4 - Nutrition and cancer: study of molecular, proteomic and metabolomic aspects of experimental model of cachexia, AP.TEM
Associated scholarship(s):22/07126-9 - Iron supplementation evaluation on cardiomyocyte functions in response to conditioned medium mimicking cancer cachexia, BE.EP.MS

Abstract

Cancer cachexia is a complex, systemic and multifactorial syndrome that cause several metabolic alterations. Skeletal muscle atrophy, the main consequence of cachexia, occurs due to protein imbalance. Protein degradation pathways can be activated by the Walker Factor, a cachexia-inducing protein, and by serum inflammatory cytokines, since inflammation is a common characteristic of cachexia. Cachexia can also affect others organs, besides skeletal muscle. Cardiac alterations in patients with cancer cachexia, known as "cardiac cachexia", have been widely observed, but often underestimated and insufficient studied. In experimental models of cancer cachexia, it was observed changes in cardiac tissue, such as mitochondrial dysfunction and changes in sarcomeric proteins. In addition, cancer cachexia could affect cardiac cell cycle, which may result in severe heart failure. In previous studies, nutritional supplementation with leucine, one of the three branched-chain amino acids, ameliorated cardiac damage due to cachexia, and changed the pathways that favored mitochondrial biogenesis in skeletal muscle. Considering the role of nutritional factors involved in the signaling pathways, the objective of this work is to evaluate the supplementation with leucine in the cell cycle, cytoskeleton and mitochondrial function of cardiac cells exposed to the serum of tumor-bearing animals, through the DNA quantification at different stages of the cell cycle, immunoflorescence assays and Western Blotting analysis of mitochondrial and sarcomeric proteins, mitochondria count, cell respiration and mitochondrial membrane potential. (AU)

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