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Volume 23
Issue 15
10.3390/ijms23158652
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Article

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

by
Chikage Mori
,
Jin-Yong Lee
,
Maki Tokumoto
and
Masahiko Satoh
*
Laboratory of Pharmaceutical Health Sciences, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya 464-8650, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2022, 23(15), 8652; https://doi.org/10.3390/ijms23158652
Submission received: 23 June 2022 / Revised: 26 July 2022 / Accepted: 2 August 2022 / Published: 3 August 2022
(This article belongs to the Special Issue Mechanisms of Heavy Metal Toxicity)
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Abstract

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.
Keywords: cadmium; kidney; PPARD; apoptosis cadmium; kidney; PPARD; apoptosis

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MDPI and ACS Style

Mori, C.; Lee, J.-Y.; Tokumoto, M.; Satoh, M. Cadmium Toxicity Is Regulated by Peroxisome Proliferator-Activated Receptor δ in Human Proximal Tubular Cells. Int. J. Mol. Sci. 2022, 23, 8652. https://doi.org/10.3390/ijms23158652

AMA Style

Mori C, Lee J-Y, Tokumoto M, Satoh M. Cadmium Toxicity Is Regulated by Peroxisome Proliferator-Activated Receptor δ in Human Proximal Tubular Cells. International Journal of Molecular Sciences. 2022; 23(15):8652. https://doi.org/10.3390/ijms23158652

Chicago/Turabian Style

Mori, Chikage, Jin-Yong Lee, Maki Tokumoto, and Masahiko Satoh. 2022. "Cadmium Toxicity Is Regulated by Peroxisome Proliferator-Activated Receptor δ in Human Proximal Tubular Cells" International Journal of Molecular Sciences 23, no. 15: 8652. https://doi.org/10.3390/ijms23158652

APA Style

Mori, C., Lee, J.-Y., Tokumoto, M., & Satoh, M. (2022). Cadmium Toxicity Is Regulated by Peroxisome Proliferator-Activated Receptor δ in Human Proximal Tubular Cells. International Journal of Molecular Sciences, 23(15), 8652. https://doi.org/10.3390/ijms23158652

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