Fibras musculares oxidativas e glicolíticas apresentam resposta inflamatória e alterações bioenergéticas peculiares após uma contusão musculoesquelética em ratos

Abstract

Muscle contusion represents a type of stress that disrupts cell homeostasis. Characterized by traumatic lesion, that impair the availability of oxygen (O2) in the tissue, promotes an increase in the production of reactive oxygen species (ROS), an increase in Ca2 + intra mitochondrial, consequent opening of the transition pore of the mitochondrial membrane and signaling for cell death and / or mitophagy. Nowadays, it is known that the increase in ROS triggers activation of pro-inflammatory pathways and proteins. However, the specific responses of different types of muscle fibers are little addressed in the literature. Considering the important role of mitochondrial in muscle tissue function. Little is known about the relation between the bioenergetics alters and mitochondrial functionality triggered in different types of muscle fiber by injury, such as the contusion, and how this mitochondrial dysfunction will affect the immediate inflammatory response developed by muscle. Thus, the objective of this study was to elucidate the possible mitochondrial mechanisms after a muscle contusion injury in the fibers of oxidative, mixed and glycolytic metabolism (Article 1), and the signaling pathways of inflammatory response and cell death related to mitochondria dysfunction and oxidative stress immediately after musculoskeletal injury in different types of muscle fibers (Manuscript 1).The results in article 1, demonstrate that the contusion led to different forms of mitochondrial dysfunction in each type of muscle fibers: increased O2 flux of oxidative fibers when stimulated by complex substrates I + II. On the other hand, increased the production of hydrogen peroxide (H2O2) when compared to control fibers and reduced citrate synthase activity. Surprisingly, the injury increased oxygen consumption in the mixed fibers in the synthesis of OXPHOS and ATP, and H2O2 production, however, reduced Ca2 + uptake. Glycolytic fibers did not affect the oxygen flux coupled to the synthesis of ATP, and citrate synthase and lactate dehydrogenase activity, but reduced Ca2 + uptake. In manuscript 1, in our study it involved the response over two hours of the contusion in the different types of muscle fibers (Manuscript 1) we showed an increase in the inflammatory pathway through the TLR4 receptor, going through an increase in the electron escape (LEAK state in oxidative and mixed fibers; and ROX in glycolytic fibers), due to an increase in pro-inflammatory cytokine gene expression and important markers of mitochondrial dysfunction (BAX and Caspase 3), culminating in increase of gene expression and TLR4 protein. Therefore, we demonstrate distinct mitochondrial responses between different muscle fibers, indicating that mitochondrial dynamics are related to flexibilities in metabolism and that as reactive oxygen species directly affect physiology and normal function. And the dysfunction of mitochondrial bioenergetics possibly interferes with the activation of the TRL4 pathway, increasing the presence of cytokines in oxidative and glycolytic / oxidative fibers.