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- Title
Cisplatin Induces Kidney Cell Death via ROS-dependent MAPK Signaling Pathways by Targeting Peroxiredoxin I and II in African Green Monkey (Chlorocebus aethiops sabaeus) Kidney Cells.
- Authors
HUI-NA ZHANG; WAN-QIU XIAO; DONG HUN LEE; NAN LI; YAO-YUAN FENG; TING SU; HAN-YU GU; IJOO YOON; HAIYOUNG JUNG; KYUNG HO LEE; HEE JUN CHO; YING-HAO HAN; HU-NAN SUN; TAEHO KWON
- Abstract
Background/Aim: Cisplatin [cis-diamminedichloroplatinum(II), CDDP] is a widely used and effective antitumor drug in clinical settings, notorious for its nephrotoxic side effects. This study investigated the mechanisms of CDDPinduced damage in African green monkey kidney (Vero) cells, with a focus on the role of Peroxiredoxin I (Prx I) and Peroxiredoxin II (Prx II) of the peroxiredoxin (Prx) family, which scavenge reactive oxygen species (ROS). Materials and Methods: We utilized the Vero cell line derived from African green monkey kidneys and exposed these cells to various concentrations of CDDP. Cell viability, apoptosis, ROS levels, and mitochondrial membrane potential were assessed. Results: CDDP significantly compromised Vero cell viability by elevating both cellular and mitochondrial ROS, which led to increased apoptosis. Pretreatment with the ROS scavenger Nacetyl-L-cysteine (NAC) effectively reduced CDDP-induced ROS accumulation and subsequent cell apoptosis. Furthermore, CDDP reduced Prx I and Prx II levels in a doseand time-dependent manner. The inhibition of Prx I and II exacerbated cell death, implicating their role in CDDPinduced accumulation of cellular ROS. Additionally, CDDP enhanced the phosphorylation of MAPKs (p38, ERK, and JNK) without affecting AKT. The inhibition of these pathways significantly attenuated CDDP-induced apoptosis. Conclusion: The study highlights the involvement of Prx proteins in CDDPinduced nephrotoxicity and emphasizes the central role of ROS in cell death mediation. These insights offer promising avenues for developing clinical interventions to mitigate the nephrotoxic effects of CDDP.
- Subjects
CHLOROCEBUS; CISPLATIN; MITOGEN-activated protein kinases; PEROXIREDOXINS; KIDNEY cell culture
- Publication
In Vivo, 2024, Vol 38, Issue 2, p630
- ISSN
0258-851X
- Publication type
Article
- DOI
10.21873/invivo.13482