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

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.

Upconversion Nanoparticle-Based Cell Membrane-Coated cRGD Peptide Bioorthogonally Labeled Nanoplatform for Glioblastoma Treatment

“…47 As heavy metals are generally toxic, their accumulation may cause acute or chronic oxidative stress, lead to excessive ROS production. 48 By covering CdS/ZnS nanoparticles with the PEGylated cRGD liganddecorated CCM, targeted delivery of nanoparticles to glioblastoma was achieved. Therefore, accumulation of CdS/ ZnS nanoparticles in glioblastoma would result in better treatment efficacy and reduced side effects.…”

“…Cadmium is a kind of heavy metal . As heavy metals are generally toxic, their accumulation may cause acute or chronic oxidative stress, lead to excessive ROS production . By covering CdS/ZnS nanoparticles with the PEGylated cRGD ligand-decorated CCM, targeted delivery of nanoparticles to glioblastoma was achieved.…”

Anthocyanins from Lycium ruthenicum Murray Mitigate Cadmium-Induced Oxidative Stress and Testicular Toxicity by Activating the Keap1/Nrf2 Signaling Pathway

“…Many studies have reported that the mechanisms underlying Cd-induced reproductive toxicity are complex [ 16 , 17 , 18 , 19 ]. The presence of Cd significantly increases the expression of blood vessel-related proteins, including CD31, NG2, αSMA, and caveolin-1, which stimulate abnormal proliferation of vascular endothelial cells and result in high blood pressure and vascular damage [ 20 ].…”