LEONARDO JENSEN SOCAS
Projetos de Pesquisa
Unidades Organizacionais
LIM/59 - Laboratório de Biologia Celular, Hospital das Clínicas, Faculdade de Medicina
2 resultados
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- Anserine is expressed in human cardiac and skeletal muscles(2023) GONCALVES, Livia de Souza; PEREIRA, Wagner Ribeiro; SILVA, Rafael Pires da; YAMAGUCHI, Guilherme Carvalho; CARVALHO, Victor Henrique; VARGAS, Bianca Scigliano; JENSEN, Leonardo; MEDEIROS, Marisa Helena Gennari de; ROSCHEL, Hamilton; ARTIOLI, Guilherme GianniniWe evaluated whether anserine, a methylated analog of the dipeptide carnosine, is present in the cardiac and skeletal muscles of humans and whether the CARNMT1 gene, which encodes the anserine synthesizing enzyme carnosine-N-methyltransferase, is expressed in human skeletal muscle. We found that anserine is present at low concentrations (low micromolar range) in both cardiac and skeletal muscles, and that anserine content in skeletal muscle is similar to 15 times higher than in cardiac muscle (cardiac muscle: 10.1 +/- 13.4 mu mol.kg(-1) of dry muscle, n = 12; skeletal muscle: 158.1 +/- 68.5 mu mol.kg(-1) of dry muscle, n = 11, p < 0.0001). Anserine content in the heart was highly variable between individuals, ranging from 1.4 to 45.4 mu mol.kg(-1) of dry muscle, but anserine content was not associated with sex, age, or body mass. We also showed that CARNMT1 gene is poorly expressed in skeletal muscle (n = 10). This is the first study to demonstrate that anserine is present in the ventricle of the human heart. The presence of anserine in human heart and the confirmation of its expression in human skeletal muscle open new avenues of investigation on the specific and differential physiological functions of histidine dipeptides in striated muscles.
- Histidine dipeptides are key regulators of excitation-contraction coupling in cardiac muscle: Evidence from a novel CARNS1 knockout rat model(2021) GONCALVES, Livia de Souza; SALES, Lucas Peixoto; SAITO, Tiemi Raquel; CAMPOS, Juliane Cruz; FERNANDES, Alan Lins; NATALI, Jose; JENSEN, Leonardo; ARNOLD, Alexandre; RAMALHO, Lisley; BECHARA, Luiz Roberto Grassmann; ESTECA, Marcos Vinicius; CORREA, Isis; SANT'ANNA, Diogo; CERONI, Alexandre; MICHELINI, Lisete Compagno; GUALANO, Bruno; TEODORO, Walcy; CARVALHO, Victor Henrique; VARGAS, Bianca Scigliano; MEDEIROS, Marisa Helena Gennari; BAPTISTA, Igor Luchini; IRIGOYEN, Maria Claudia; SALE, Craig; FERREIRA, Julio Cesar Batista; ARTIOLI, Guilherme GianniniHistidine-containing dipeptides (HCDs) are abundantly expressed in striated muscles. Although important properties have been ascribed to HCDs, including H+ buffering, regulation of Ca2+ transients and protection against oxidative stress, it remains unknown whether they play relevant functions in vivo. To investigate the in vivo roles of HCDs, we developed the first carnosine synthase knockout (CARNS1-/-) rat strain to investigate the impact of an absence of HCDs on skeletal and cardiac muscle function. Male wild-type (WT) and knockout rats (4 months-old) were used. Skeletal muscle function was assessed by an exercise tolerance test, contractile function in situ and muscle buffering capacity in vitro. Cardiac function was assessed in vivo by echocardiography and cardiac electrical activity by electrocardiography. Cardiomyocyte contractile function was assessed in isolated cardiomyocytes by measuring sarcomere contractility, along with the determination of Ca2+ transient. Markers of oxidative stress, mitochondrial function and expression of proteins were also evaluated in cardiac muscle. Animals were supplemented with carnosine (1.8% in drinking water for 12 weeks) in an attempt to rescue tissue HCDs levels and function. CARNS1-/- resulted in the complete absence of carnosine and anserine, but it did not affect exercise capacity, skeletal muscle force production, fatigability or buffering capacity in vitro, indicating that these are not essential for pH regulation and function in skeletal muscle. In cardiac muscle, however, CARNS1-/- resulted in a significant impairment of contractile function, which was confirmed both in vivo and ex vivo in isolated sarcomeres. Impaired systolic and diastolic dysfunction were accompanied by reduced intracellular Ca2+ peaks and slowed Ca2+ removal, but not by increased markers of oxidative stress or impaired mitochondrial respiration. No relevant increases in muscle carnosine content were observed after carnosine supplementation. Results show that a primary function of HCDs in cardiac muscle is the regulation of Ca2+ handling and excitation-contraction coupling.