Bicarbonate Increases Ischemia-Reperfusion Damage by Inhibiting Mitophagy

Autor(es)

Queliconi, Bruno B. ; Kowaltowski, Alicia J. ; Gottlieb, Roberta A.

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 11, n. 12 DEC 14 2016.
• Citações Web of Science: 7

Resumo

During an ischemic event, bicarbonate and CO2 concentration increase as a consequence of O-2 consumption and lack of blood flow. This event is important as bicarbonate/CO2 is determinant for several redox and enzymatic reactions, in addition to pH regulation. Until now, most work done on the role of bicarbonate in ischemia-reperfusion injury focused on pH changes; although reperfusion solutions have a fixed pH, cardiac resuscitation protocols commonly employ bicarbonate to correct the profound acidosis associated with respiratory arrest. However, we previously showed that bicarbonate can increase tissue damage and protein oxidative damage independent of pH. Here we show the molecular basis of bicarbonate- induced reperfusion damage: the presence of bicarbonate selectively impairs mitophagy, with no detectable effect on autophagy, proteasome activity, reactive oxygen species production or protein oxidation. We also show that inhibition of autophagy reproduces the effects of bicarbonate in reperfusion injury, providing additional evidence in support of this mechanism. This phenomenon is especially important because bicarbonate is widely used in resuscitation protocols after cardiac arrest, and while effective as a buffer, may also contribute to myocardial injury. (AU)

• Processo FAPESP: 10/51906-1 - Bioenergética, transporte iônico, balanço redox e metabolismo de DNA em mitocôndrias
• Beneficiário: Alicia Juliana Kowaltowski
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 13/07937-8 - Redoxoma
• Beneficiário: Ohara Augusto
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 13/07292-7 - Efeitos de bicarbonato na mitofagia durante isquemia-reperfusão
• Beneficiário: Bruno Barros Queliconi
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado Direto
• Processo FAPESP: 09/50168-0 - Efeitos bioenergéticos e redox do pós-condicionamento cardíaco
• Beneficiário: Bruno Barros Queliconi
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto