Akademik Veri Yönetim Sistemi
TURKISH JOURNAL OF BIOCHEMISTRY-TURK BIYOKIMYA DERGISI, 2024 (SCI-Expanded)
Objectives: Mutations detected in the AVPR2 gene (arginine vasopressin type 2 receptor) are known to cause nephrogenic diabetes insipidus (NDI). Several pharmacological chaperones (PCs) target misfolded AVPR2 proteins and rescue them from the quality control system of the cell. In this study, we investigated the effect of YM087 and VPA985, which are PCs, on T273M-AVPR2 mutant that are known to cause NDI. Methods: The total and cell surface expressions of T273M in COS-1 cells were measured by sandwich ELISA and flow cytometry after the cells were treated with YM087 and VPA985 separately. In addition, the cAMP accumulation assay was performed. Results: It was observed that VPA985 treatment significantly increased the cell surface expression and slightly increased the maximum cAMP response of T273M. Both YM087 and VPA985 decreased the ligand concentrations which were responsible for making half of the maximum response of the T273M mutant receptor. Conclusions: PCs have different potential effects on different AVPR2 mutants. Therefore, studying the effectiveness of PCs in rescuing AVPR2 mutants and making them functional again may contribute to the development of new therapeutic strategies.