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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Bicarbonate Increases Ischemia-Reperfusion Damage by Inhibiting Mitophagy

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Queliconi, Bruno B. ; Kowaltowski, Alicia J. ; Gottlieb, Roberta A.
Total Authors: 3
Document type: Journal article
Source: PLoS One; v. 11, n. 12 DEC 14 2016.
Web of Science Citations: 7

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)

FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
Grantee:Ohara Augusto
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 13/07292-7 - Effect of bicarbonate on mitophagy during ischemia/reperfusion
Grantee:Bruno Barros Queliconi
Support type: Scholarships abroad - Research Internship - Doctorate (Direct)
FAPESP's process: 10/51906-1 - Mitochondrial bioenergetics, ion transport, redox state and DNA metabolism
Grantee:Alicia Juliana Kowaltowski
Support type: Research Projects - Thematic Grants