Cadmium Toxicity Is Regulated by Peroxisome Proliferator-Activated Receptor δ in Human Proximal Tubular Cells

• Published in: International journal of molecular sciences Vol. 23; no. 15; p. 8652
• Main Authors: Mori, Chikage, Lee, Jin-Yong, Tokumoto, Maki, Satoh, Masahiko
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.08.2022; MDPI
• Subjects: Apoptosis; Cadmium; Caspase-3; Cell growth; Cytotoxicity; DNA chips; DNA microarrays; Fatty acids; Gene expression; Genes; Glucose; Heavy metals; kidney; Liver; Metabolism; Peroxisome proliferator-activated receptors; PPARD; Toxicity; Transcription factors; Japan
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23158652

Cadmium (Cd) is a toxic heavy metal that is widely present in the environment. Renal proximal tubule disorder is the main symptom of Cd chronic poisoning. Our previous study demonstrated that Cd inhibits the total activities of peroxisome proliferator-activated receptor (PPAR) transcription factors in human and rat proximal tubular cells. In this study, we investigated the involvement of PPAR in Cd renal toxicity using the HK-2 human proximal tubular cell line. Among PPAR isoform genes, only PPARD knockdown significantly showed resistance to Cd toxicity in HK-2 cells. The transcriptional activity of PPARδ was decreased not only by PPARD knockdown but also by Cd treatment. DNA microarray analysis showed that PPARD knockdown changed the expression of apoptosis-related genes in HK-2 cells. PPARD knockdown decreased apoptosis signals and caspase-3 activity induced by Cd treatment. PPARD knockdown did not affect the intracellular Cd level after Cd treatment. These results suggest that PPARδ plays a critical role in the modification of susceptibility to Cd renal toxicity and that the apoptosis pathway may be involved in PPARδ-related Cd toxicity.