Transient response of serpinA3 during cellular stress
Por:
Sanchez-Navarro, Andrea, Murillo-de-Ozores A.R., Perez-Villalva, Rosalba, Linares, Nadyeli, Carbajal-Contreras, Hector, Flores, Maria Elena, Gamba, Gerardo, Castañeda-Bueno M., Bobadilla, Norma A.
Publicada:
1 mar 2022
Resumen:
We demonstrated that serpinA3c/k relocates from the cytoplasm to the
apical tubular membrane (ATM) in chronic kidney disease (CKD),
suggesting its secretion in luminal space in pathophysiological
contexts. Here, we studied serpinA3c/k expression and secretion under
different stressful conditions in vitro and in vivo. HEK-293 cells were
transfected with a FLAG-tagged serpinA3c/k clone and exposed to H2O2 or
starvation. Both stressors induced serpinA3c/k secretion but with a
higher molecular weight. Glycanase treatment established that
serpinA3c/k is glycosylated. Site-directed mutagenesis for each of the
four glycosylation sites was performed. During cellular stress,
serpinA3c/k secretion increased with each mutant except in the quadruple
mutant. In rats and patients suffering acute kidney injury (AKI), an
atypical urinary serpinA3c/k excretion (uSerpinA3c/k) was observed. In
rats with AKI, the greater the induced kidney damage, the greater the
uSerpinA3 c/k, together with relocation toward ATM. Our findings show
that: (1) serpinA3c/k is glycosylated and secreted, (2) serpinA3c/k
secretion increases during cellular stress, (3) its appearance in urine
reveals a pathophysiological state, and (4) urinary serpinA3 excretion
could become a potential biomarker for AKI.
Filiaciones:
Sanchez-Navarro, Andrea:
Molecular Physiology Unit, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico
Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Murillo-de-Ozores A.R.:
Molecular Physiology Unit, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico
Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Perez-Villalva, Rosalba:
Molecular Physiology Unit, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico
Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Linares, Nadyeli:
Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Carbajal-Contreras, Hector:
Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Combined Studies Program in Medicine MD/PhD (PECEM), Facultad de Medicina, UNAM, Mexico City, Mexico
Flores, Maria Elena:
Department of Molecular Biology and Biotechnology, Instituto de investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico
Gamba, Gerardo:
Molecular Physiology Unit, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico
Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Castañeda-Bueno M.:
Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Bobadilla, Norma A.:
Molecular Physiology Unit, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico
Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
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