| Grant number: | 14/11948-8 |
| Support Opportunities: | Research Grants - Young Investigators Grants |
| Field of knowledge: | Health Sciences - Physical Education |
| Principal Investigator: | Guilherme Giannini Artioli |
| Grantee: | Guilherme Giannini Artioli |
| Host Institution: | Escola de Educação Física e Esporte (EEFE). Universidade de São Paulo (USP). São Paulo , SP, Brazil |
| Associated researchers: | Antonio Herbert Lancha Junior ; Bruno Gualano ; Edilamar Menezes de Oliveira ; Julio Cesar Batista Ferreira ; Patricia Chakur Brum |
Abstract
Carnosine (ß-alanyl-L-histidine) is a dipeptide abundantly found in skeletal and cardiac muscles as well as in excitable tissues, although the physiological roles played by carnosine and its methylated analogues are still poorly understood. Evidence indicates that carnosine acts as a physico-chemical buffer during intense efforts, which is corroborated by the performance improvements observed following ²-alanine supplementation. Alternatively, carnosine has been suggested to improve the calcium sensitivity to the contractile apparatus and to protect cellular structures from oxidative damage. In this project, we propose to develop a new knockout rat model with a non-functional CARNS1 gene, leading to the complete absence of carnosine/anserine in their tissues. A successful model is critical to the subsequent aims of the proposed programme of work, which is to investigate the physiological roles of carnosine/anserine and their relevance to exercise and training responses. The knockout rats will be outsourced from an external company and the colony will be established at our Institution, allowing a completely new research line in our University, initially comprising 5 distinct and novel studies that have the potential to answer fundamental questions in this research área but also to hypothesis generate for future reserach programmes. Our initial 5 studies are designed to provide the answers to key fundamental questions that underpin the potential physiological roles of carnosine: 1) to evaluate the impact of carnosine/anserine absence on isolated skeletal muscle contractile proteins, morphology, buffering capacity, expression of genes involved in carnosine metabolism, expression and phosphorylation of calcium-handling proteins and the physiological responses to contraction until exhaustion; 2) to evaluate the impact of carnosine/anserine absence on tolerance to high-intensity exercise, as well as on muscle metabolic responses to exercise, with measures including blood pH and lactate, muscle pH and lactate, muscle glycogen and activity of energy-metabolism key-enzymes; 3) to evaluate the impact of carnosine/anserine absence on total non-enzymatic anti-oxidant capacity of the skeletal muscle and the protection to oxidative damage induced by high-volume aerobic training, with measures including advanced glycation products, markers of cellular damage and protein-bound carbonyl groups; 4) to evaluate the impact of carnosine/anserine absence on left ventricle contractile function (assessed in-vivo and ex-vivo) and miocardial contractile properties (assessed in-vitro), with parallel measures of the calcium transient; 5) to evaluate whether/not carnosine supplementation is able to replenish muscle carnosine content and whether/not this is accompanied by a regain of function, assessing the same functional parameters described above for skeletal and cardiac muscles. In all studies, a group of knockout rats will be compared with a group of age- and body mass-matched wild-type controls. (AU)
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