Transient response of serpinA3 during cellular stress.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2022 Mar

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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 H2 O2 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. © 2022 Federation of American Societies for Experimental Biology.

Citation

Andrea Sánchez-Navarro, Adrián Rafael Murillo-de-Ozores, Rosalba Pérez-Villalva, Nadyeli Linares, Héctor Carbajal-Contreras, María Elena Flores, Gerardo Gamba, María Castañeda-Bueno, Norma A Bobadilla. Transient response of serpinA3 during cellular stress. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2022 Mar;36(3):e22190