SerpinA3K Deficiency Reduces Oxidative Stress in Acute Kidney Injury
Por:
Gonzalez-Soria, Isaac, Soto-Valadez, Axel D. D., Martinez-Rojas, Miguel Angel, Ortega-Trejo, Juan Antonio, Perez-Villalva, Rosalba, Gamba, Gerardo, Sanchez-Navarro, Andrea, Bobadilla, Norma A. A.
Publicada:
25 abr 2023
Resumen:
We previously showed that SerpinA3K is present in urine from rats and
humans with acute kidney injury (AKI) and chronic kidney disease (CKD).
However, the specific role of SerpinA3K during renal pathophysiology is
unknown. To begin to understand the role of SerpinA3K on AKI,
SerpinA3K-deficient (KOSA3) mice were studied 24 h after inducing
ischemia/reperfusion (I/R) and compared to wild type (WT) mice. Four
groups were studied: WT+S, WT+IR, KOSA3+S, and KOSA3+IR. As expected,
I/R increased serum creatinine and BUN, with a GFR reduction in both
genotypes; however, renal dysfunction was ameliorated in the KOSA3+IR
group. Interestingly, the increase in UH2O2 induced by I/R was not
equally seen in the KOSA3+IR group, an effect that was associated with
the preservation of antioxidant enzymes' mRNA levels. Additionally,
FOXO3 expression was initially greater in the KOSA3 than in the WT
group. Moreover, the increase in BAX protein level and the decrease in
Hif1a and Vegfa induced by I/R were not observed in the KOSA3+IR group,
suggesting that these animals have better cellular responses to hypoxic
injury. Our findings suggest that SerpinA3K is involved in the renal
oxidant response, HIF1a/VEGF pathway, and cell apoptosis.
Filiaciones:
Gonzalez-Soria, Isaac:
Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico
Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, 14080, Mexico
PECEM (MD/PhD), Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico
Univ Nacl Autonoma Mexico, Mol Physiol Unit, Inst Invest Biomed, Mexico City 04510, Mexico
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Nephrol & Mineral Metab, Mexico City 14080, Mexico
Univ Nacl Autonoma Mexico, Fac Med, PECEM MD PhD, Mexico City 04510, Mexico
Soto-Valadez, Axel D. D.:
Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico
Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, 14080, Mexico
Univ Nacl Autonoma Mexico, Mol Physiol Unit, Inst Invest Biomed, Mexico City 04510, Mexico
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Nephrol & Mineral Metab, Mexico City 14080, Mexico
Martinez-Rojas, Miguel Angel:
Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico
Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, 14080, Mexico
Univ Nacl Autonoma Mexico, Mol Physiol Unit, Inst Invest Biomed, Mexico City 04510, Mexico
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Nephrol & Mineral Metab, Mexico City 14080, Mexico
Ortega-Trejo, Juan Antonio:
Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico
Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, 14080, Mexico
Univ Nacl Autonoma Mexico, Mol Physiol Unit, Inst Invest Biomed, Mexico City 04510, Mexico
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Nephrol & Mineral Metab, Mexico City 14080, Mexico
Perez-Villalva, Rosalba:
Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico
Univ Nacl Autonoma Mexico, Mol Physiol Unit, Inst Invest Biomed, Mexico City 04510, Mexico
Gamba, Gerardo:
Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico
Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, 14080, Mexico
Univ Nacl Autonoma Mexico, Mol Physiol Unit, Inst Invest Biomed, Mexico City 04510, Mexico
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Nephrol & Mineral Metab, Mexico City 14080, Mexico
Sanchez-Navarro, Andrea:
Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico
Univ Nacl Autonoma Mexico, Mol Physiol Unit, Inst Invest Biomed, Mexico City 04510, Mexico
Bobadilla, Norma A. A.:
Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico
Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, 14080, Mexico
Univ Nacl Autonoma Mexico, Mol Physiol Unit, Inst Invest Biomed, Mexico City 04510, Mexico
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Nephrol & Mineral Metab, Mexico City 14080, Mexico
gold, All Open Access; Gold
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