Efeitos da privação de sono na homeostase e metabolismo do cálcio em esplenócitos de camundongos

• Ano de defesa: 2011
• Autor(a) principal: Lungato, Lisandro [UNIFESP]
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Disfunção mitocondrial; Camundongos; Esplenócitos; Estresse oxidativo; Privação de sono; Sinalização do Ca2+; Mitochondrial disfunction; Mice; Oxidative stress; Sleep deprivation; Signaling of Ca2+
• Link de acesso: http://repositorio.unifesp.br/handle/11600/9405

Sleep is an important physiological event that directly influences health and is related to the immune system in which calcium acts as an important messenger. In this study, we performed measurements of cytosolic calcium mobilization in living cells in order to understand the changes in this ion signaling in immune cells from mice after different periods of sleep deprivation. Splenocytes of mice deprived of sleep for various periods (12 to 72 hours) showed a progressive loss of the intracellular calcium maintenance from the endoplasmic reticulum store and a commitment of transient calcium buffering by mitochondria. These data were confirmed by changes in the performance of calcium channels SOCE and STIM1 and in the integrity of lysosomal and mitochondrial physiology. These results were corroborated by the increase in activity of antioxidant enzymes such as mitochondrial and cytosolic superoxide dismutase, which reinforces the idea that the disruption in the integrity of mitochondria and lysosomes possibly occurred by uncontrolled generation of oxidative stress. The reduction of catalase activity suggests involvement in cellular integrity, since excess of calcium and free radicals probably compromise cell signaling. Moreover, deficient immune response was observed when a group of mice was allowed to sleep for 24 and 48 hours of sleep deprivation for 72 hours, followed by infection with malaria parasites (Plasmodium chabaudi). The involvement of the immune cells was confirmed by the reduction in the total population of cells in the spleen and, specifically, the population of B lymphocytes. These new data suggest that sleep deprivation affects calcium signaling probably by a stress in the endoplasmic reticulum, mitochondria and lysosomes, leading to an insufficient supply of calcium to signaling events and consequent intracellular damage. These data confirm previously described mechanisms of immunosuppressive effects of sleep loss.