Cry2 Alleviates Cisplatin-Induced Cytotoxicity in Mouse Renal Cortex Tubular Cell Lines.

Abstract

Cisplatin is a platinum-based drug that is widely used to treat various types of cancer. However, cisplatin is known to cause severe adverse effects, such as nephrotoxicity and ototoxicity. Clock genes, such as Bmal1 and Clock, regulate cisplatin-related homeostasis genes, such as Oct2 and Mate1. Although these clock genes may be involved in cisplatin-induced nephrotoxicity, their associations with other clock genes remain unclear. The aim of the present study was to investigate whether seven clock genes (Ciart, cryptochrome 1 (Cry1), Cry2, Npas2, Per1, Per2, and Per3) regulate cisplatin-induced renal toxicity in a renal cortex tubule cell line (MuRTE61). Cisplatin treatment decreases MuRTE61 cell viability in a dose-dependent manner. Cry2 expression levels increased after treatment with cisplatin for 24 h. Notably, Cry2 overexpression alleviated cisplatin-induced suppression of cell proliferation, apoptosis, and platinum content in MuRTE61 cells. Moreover, Cry2 overexpression upregulated the efflux-related transporters (Atp7a and Mrp2). These results suggest that Cry2 protects against cisplatin toxicity by reducing Pt accumulation and increasing the expression of Atp7a and Mrp2.