Beiral 2014 Cell Transplant

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Beiral HJ, Rodrigues-Ferreira C, Fernandes AM, Gonsalez SR, Mortari NC, Takiya CM, Sorenson MM, Figueiredo-Freitas C, Galina A, Vieyra A (2014) The impact of stem cells on electron fluxes, proton translocation and ATP synthesis in kidney mitochondria after ischemia/reperfusion. Cell Transplant 23:207-20.

» PMID: 23211430

Beiral HJ, Rodrigues-Ferreira C, Fernandes AM, Gonsalez SR, Mortari NC, Takiya CM, Sorenson MM, Figueiredo-Freitas C, Galina A, Vieyra A (2014) Cell Transplant

Abstract: Tissue damage by ischemia/reperfusion (I/R) results from a temporary cessation of blood flow followed by restoration of circulation. The injury depresses mitochondrial respiration, increases the production of reactive oxygen species (ROS), decreases the mitochondrial transmembrane potential and stimulates invasion by inflammatory cells. The primary objective of this work was to address the potential use of bone marrow stem cells (BMSCs) to preserve/restore mitochondrial function in the kidney after I/R. Mitochondria from renal proximal tubule cells were isolated by differential centrifugation from rat kidneys subjected to I/R (clamping of renal arteries followed by release of circulation after 30 min), without or with subcapsular administration of BMSCs. Respiration starting from mitochondrial complex II was strongly affected following I/R. However, when BMSCs were injected before ischemia or together with reperfusion, normal electron fluxes, electrochemical gradient for protons and ATP synthesis were almost completely preserved, and mitochondrial ROS formation occurred at low rate. In homogenates from cultured renal cells transiently treated with antimycin A, the co-culture with BMSCs induced a remarkable increase in protein S-nitrosylation that was similar to that found in mitochondria isolated from I/R rats, evidence that BMSCs protected against both superoxide anion and peroxynitrite. Labeled BMSCs migrated to damaged tubules, suggesting that the injury functions as a signal to attract and host the injected BMSCs. Structural correlates of BMSC injection in kidney tissue included stimulus of tubule cell proliferation, inhibition of apoptosis and decreased inflammatory response. Histopathological analysis demonstrated a score of complete preservation of tubular structures by BMSCs, associated with normal plasma creatinine and urinary osmolality. The key findings shed light on the mechanisms that explain, at the mitochondrial level, how stem cells prevent damage by I/R. The action of BMSCs on mitochondrial functions raises the possibility that autologous BMSCs may help prevent I/R injuries associated with transplantation and acute renal diseases.

Keywords: Kidney mitochondria; Bone marrow stem cells; Ischemia/Reperfusion; Mitochondrial respiration; ATP synthesis

O2k-Network Lab: BR Rio de Janeiro Galina A

Labels: MiParea: Respiration, mt-Medicine 

Stress:Ischemia-reperfusion  Organism: Rat  Tissue;cell: Kidney, Stem cells  Preparation: Isolated mitochondria 

Coupling state: LEAK, OXPHOS, ET  Pathway:HRR: Oxygraph-2k