Both depression and cancer are related to a dysregulation of inflammatory and immune pathways. Indeed, depression is associated with increased expression of interferon-γ, interleukin-1β, and tumor necrosis factor α (TNF-α). In contrast, reductions of the activity of major histocompatibility complex protein molecules - class I and class II and natural killer cells are also observed. Similarly, cancers present elevated levels of TNF-α, reduced major histocompatibility complex class I and II, and natural killer cells. Indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme of the tryptophan catabolite (TRYCAT) pathway, is induced by interferon-γ, interleukin-6, TNF-α, and oxidative stress. IDO catabolizes tryptophan, the amino acid precursor of serotonin and melatonin, to the metabolites collectively called TRYCATs. TRYCAT pathway activation is accompanied by downregulation of immune cell proliferation, function, and survival. The increase in IDO activity in tumor microenvironments is related to tumor cell escape from immune surveillance. Despite the evidence of inflammatory mechanisms underlying cancer and depression, it is important to emphasize that both diseases are heterogeneous and, as such, inflammatory mechanisms may not be relevant to all patients. Thus, the purpose of this review is to examine whether detrimental TRYCATs - synthesis of which increases in depression and cancer - are a pathophysiological link between the two diseases, and whether IDO is a potential pharmacological target for the treatment of the comorbid depression and cancer.
Introdução: A análise dos diversos fatores genéticos, principalmente os relacionados aos polimorfismos de DNA, têm sido investigados na busca de uma melhor compreensão dos mecanismos relacionados à hipertrofia e força muscular. Dentre os diversos genes polimórficos relacionados ao tema estão a miostatina e o gene α-actinina-3 (ACTN3).Objetivo: Avaliar a modulação do gene da miostatina na hipertrofia muscular esquelética e do gene ACTN3 na regulação dos níveis de força.Métodos: Estudo de revisão integrativa no qual foram pesquisados artigos que tivessem avaliado a modulação genética da hipertrofia muscular esquelética e da força. Fizeram parte desta investigação estudos originais e de revisão, publicados em português, inglês e espanhol, entre os anos de 1995 a 2017, selecionados nas bases de dados SciELO e Pubmed, utilizando-se três conjuntos de intersecção de termos de busca bibliográfica em português: a) “miostatina” e “hipertrofia muscular esquelética” e/ou “genética”; e b) “exercício físico” ou “treinamento aeróbico” ou “treinamento de força” ou “rendimento esportivo” e “ACTN3” e/ou “força muscular” e/ou genética. Em inglês: a) “myostatin”and “skeletal muscle hypertrophy” and/or genetics; and b) “physical exercise” and “aerobic training”, strength training, sports performance) and “ACTN3” “muscular strength” and/or “genetic”. E em espanhol: “miostatina” y “hipertrofia muscular esquelética” y/o genética; y b) “ejercicio físico” o “entrenamiento aeróbico” o “entrenamiento de fuerza” o “rendimiento desportivo) y “ACTN3” o “fuerza muscular” y/o genética”.Resultados e Discussão: Os estudos apontaram: a) associação do genótipo RR577 do ACTN3 com a força e o tamanho da área de secção transversa do músculo esquelético; b) correlação do alelo R com fibras glicolíticas de contração rápida e níveis médios de testosterona significativamente mais elevados; e c) o polimorfismo do ACTN3 está relacionado ao treinamento de alta intensidade. As evidências apontaram que a miostatina atua na inibição da hipertrofia muscular esquelética, e também pode ser modulada geneticamente pelo exercício físico.Conclusão: A literatura aponta evidências de que o polimorfismo do ACNT3 está relacionado com o treinamento de alta intensidade, ressaltando que, segundo os resultados dos estudos, houve correlação do alelo R, com fibras glicolíticas de contração rápida e com os níveis de testosterona significativamente mais elevados. Sendo assim, o gene ACTN3 está correlacionado com o desenvolvimento da força muscular e a folistatina, proteína antagônica da miostatina, está associada ao aumento da massa muscular. Genetic Modulation of Myostatin and Actn3 Gene in Muscular Hypertrophy and Force: an Integrative ReviewIntroduction: The analysis of several genetic factors, especially those related to DNA polymorphisms, has been investigated in the search for a better understanding of the mechanisms related to hypertrophy and muscle strength. Among the several polymorphic genes related to the subject are myostatin and ACTN3.Objective: To evaluate the modulation of the myostatin gene in skeletal muscle hypertrophy and the ACTN3 gene in the regulation of strength levels.Methods: An integrative review study in which articles were searched that assessed the genetic modulation of skeletal muscle hypertrophy and strength. Original and review studies, published in Portuguese, English and Spanish, between 1995 and 2017, selected in the SciELO and PubMed databases, were carried out using three sets of intersection of bibliographic search: In English: a) “myostatin” and “skeletal muscle hypertrophy” and/or genetics; and b) “physical exercise” and “aerobic training”, strength training, sports performance) and “ACTN3” “muscular strength” and/or “genetic”. In Portuguese: a) “miostatina” e “hipertrofia muscular esquelética” e/ou “genética”; e b) “exercício físico” ou “treinamento aeróbico” ou “treinamento de força” ou “rendimento esportivo” e “ACTN3” e/ou “força muscular” e/ou genética. And in Spanish: “miostatina” y “hipertrofia muscular esquelética” y/o genética; y b) “ejercicio físico” o “entrenamiento aeróbico” o “entrenamiento de fuerza” o “rendimiento desportivo) y “ACTN3” o “fuerza muscular” y/o genética”.Results and Discussion: Studies indicated: a) association of RR577 genotype of ACTN3 with the strength and size of the cross-sectional area of skeletal muscle; b) correlation of the R allele with fast contracting glycolytic fibers and significantly higher mean levels of testosterone; and, c) ACTN3 polymorphism is related to high intensity training. Evidence has pointed out that myostatin acts on inhibition of skeletal muscle hypertrophy, as well as being genetically modulated by physical exercise.Conclusion: The literature showed evidence that the ACNT3 polymorphism is related to the high intensity training, emphasizing that according to the results of the studies, there was a correlation of the R allele with fast contracting glycolytic fibers and with testosterone levels higher. Thus, the ACTN3 gene is correlated with the development of muscle strength and follistatin, an antagonistic protein of myostatin, is associated with increased muscle mass. Keywords: hypertrophy, muscle strength, myostatin, polymorphism.
Background: This study examined associations between scores of depression (DEPs), thiobarbituric acid-reactive substances (TBARS), superoxide dismutase (SOD), and catalase activity (CAT) in master athletes and untrained controls. Methods: Participants were master sprinters (MS, n = 24; 50.31 ± 6.34 year), endurance runners (ER, n = 11; 51.35 ± 9.12 year), untrained middle-aged (CO, n = 13; 47.21 ± 8.61 year), and young untrained (YU, n = 15; 23.70 ± 4.02 year). CAT, SOD, and TBARS were measured in plasma using commercial kits. DEPs were measured by the Beck Depression Inventory-II. An ANOVA, Kruskal-Wallis, Pearson’s, and Spearman’s correlations were applied, with a significance level of p ≤ 0.05. Results: The CATs of MS and YU [760.4 U·μL 1 ± 170.1 U·μL 1 and 729.9 U·μL 1 ± 186.9 U·μL 1] were higher than CO and ER. The SOD levels in the YU and ER [84.20 U·mL−1 ± 8.52 U·mL−1 and 78.24 U·mL−1 ± 6.59 U·mL−1 (p < 0.0001)] were higher than CO and MS. The TBARS in CO [11.97 nmol·L−1 ± 2.35 nmol·L−1 (p < 0.0001)] was higher than in YU, MS and ER. MS had lower DEPs compared to the YU [3.60 ± 3.66 vs. 12.27 ± 9.27 (p = 0.0002)]. A negative correlation was found between CAT and DEPs for master athletes [r = −0.3921 (p = 0.0240)] and a weak correlation [r = −0.3694 (p = 0.0344)] was found between DEPs and the CAT/TBARS ratio. Conclusions: In conclusion, the training model of master sprinters may be an effective strategy for increasing CAT and reducing DEPs.
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