Caloric restriction protects livers from ischemia/reperfusion damage by preventing Ca 2+ -induced mitochondrial permeability transition.

Autor: Menezes-Filho SL; Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil. Electronic address: smenezes@iq.usp.br., Amigo I; Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil. Electronic address: iamigo@iq.usp.br., Prado FM; Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil. Electronic address: fmprado@iq.usp.br., Ferreira NC; Disciplina de Cirurgia Geral e do Trauma, Laboratório de Fisiopatologia Cirúrgica-LIM-62, Faculdade de Medicina, Universidade de São Paulo, SP, Brazil. Electronic address: natalie.chaves@gmail.com., Koike MK; Disciplina de Emergências Clínicas, Laboratório de Emergências Clinicas - LIM-51 - Faculdade de Medicina - Universidade de São Paulo, Brazil. Electronic address: mkoike@usp.br., Pinto IFD; Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil. Electronic address: isabellapinto@usp.br., Miyamoto S; Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil. Electronic address: miyamoto@iq.usp.br., Montero EFS; Disciplina de Cirurgia Geral e do Trauma, Laboratório de Fisiopatologia Cirúrgica-LIM-62, Faculdade de Medicina, Universidade de São Paulo, SP, Brazil. Electronic address: efrassonsmontero@usp.br., Medeiros MHG; Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil. Electronic address: mhgdmede@iq.usp.br., Kowaltowski AJ; Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil. Electronic address: alicia@iq.usp.br.
Jazyk: angličtina
Zdroj: Free radical biology & medicine [Free Radic Biol Med] 2017 Sep; Vol. 110, pp. 219-227. Date of Electronic Publication: 2017 Jun 19.
DOI: 10.1016/j.freeradbiomed.2017.06.013
Abstrakt: Caloric restriction (CR) promotes lifespan extension and protects against many pathological conditions, including ischemia/reperfusion injury to the brain, heart and kidney. In the liver, ischemia/reperfusion damage is related to excessive mitochondrial Ca 2+ accumulation, leading to the mitochondrial permeability transition. Indeed, liver mitochondria isolated from animals maintained on CR for 4 months were protected against permeability transition and capable of taking up Ca 2+ at faster rates and in larger quantities. These changes were not related to modifications in mitochondrial respiratory activity, but rather to a higher proportion of ATP relative to ADP in CR liver mitochondria. Accordingly, both depletion of mitochondrial adenine nucleotides and loading mitochondria with exogenous ATP abolished the differences between CR and ad libitum (AL) fed groups. The prevention against permeability transition promoted by CR strongly protected against in vivo liver damage induced by ischemia/reperfusion. Overall, our results show that CR strongly protects the liver against ischemia/reperfusion and uncover a mechanism for this protection, through a yet undescribed diet-induced change in liver mitochondrial Ca 2+ handling related to elevated intramitochondrial ATP.
(Copyright © 2017 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: