Phospholipase D1 Ameliorates Apoptosis in Chronic Renal Toxicity Caused by Low-Dose Cadmium Exposure

Abstract

Exposure to cadmium (Cd), a common heavy metal used in industry, can result in long-term chronic toxicity. It has been well characterized that kidneys are the main organs that are targeted by toxicity, which can cause apoptosis, necrosis, and atrophy of renal tubular epithelial cells. However, the molecular mechanisms associated with Cd toxicity remain unclear. In this study, the expression of renal proteins in Sprague-Dawley rats exposed to chronic Cd was analyzed with iTRAQ proteomics. Bioinformatics analysis indicated that phospholipase D1 (PLD1) was significantly underexpressed and may correlate strongly with Cd-induced chronic kidney impairment. Previous studies have shown that PLD1 promotes cell proliferation and inhibits apoptosis, indicating that PLD1 may be implicated in the pathogenesis of kidney injury induced by Cd. Studies in vivo and in vitro all demonstrate that the mRNA and protein levels of PLD1 decrease significantly both in kidney tissue and in proximal tubular cell lines exposed to Cd. Overexpression of PLD1 and its downstream product PA could ameliorate Cd-induced apoptosis. Moreover, we identified that miR-122-5p was a regulatory miRNA of PLD1. miR-122-5p was overexpressed after Cd exposure and promoted cell apoptosis by downregulating PLD1 through binding the 3′UTR of the locus at 1761–1784 nt. In conclusion, our results indicated that PLD1 and its downstream PA were strongly implicated in Cd-induced chronic kidney impairment and could be a novel player in the defense against Cd-induced nephrotoxicity.

Histomorphological and ultrastructural cadmium-induced kidney injuries and precancerous lesions in rats and screening for biomarkers

“…Humans can be exposed to Cd through contaminated food, drinking water, air, and soil [ 2 , 3 ]. Cd harms several target organs in humans, including the brain, lung, liver, bones [ 4 , 5 ], and especially the kidney [ 6 ], as Cd-induced nephrotoxicity involves apoptosis, necrosis, and atrophy of renal tubular epithelial cells [ 7 ]. In addition, the kidneys absorb approximately 50% of the total body Cd after long-term Cd exposure [ 8 ].…”

Current Levels of Environmental Exposure to Cadmium in Industrialized Countries as a Risk Factor for Kidney Damage in the General Population: A Comprehensive Review of Available Data

“…The following supporting information can be downloaded at: https: //www.mdpi.com/article/10.3390/ijms24098413/s1. References [5,17,22,37,66,72,84,126,146,149,[167][168][169][178][179][180][181][182][183][184][185][186][187][188][189][190][191] are cited in the supplementary materials.…”

Biochar and organic fertilizer drive the bacterial community to improve the productivity and quality of Sophora tonkinensis in cadmium-contaminated soil

“…Even at minimal levels of exposure, Cd can induce kidney and skeletal diseases, cardiac metabolic dysfunction, cancer, and mortality in humans ( Menahem et al, 2018 ; Hui et al, 2019 ; Rachael et al, 2019 ). Additionally, excessive Cd accumulation in the soil can disrupt the metabolic processes of plants ( Meghan et al, 2017 ; Zhu et al, 2020 ), such as protein synthesis ( Lian et al, 2015 ; Sha et al, 2019 ), nitrogen and carbohydrate metabolism ( Huang et al, 2020 ; Zhu et al, 2022 ; Cao et al, 2023 ), enzyme activation ( Chmielowska and Deckert, 2012 ; Lian et al, 2018 ; AlHuqail et al, 2023 ), photosynthesis, and chlorophyll synthesis ( Abeer et al, 2016 ; Raletsena et al, 2022 ; Tunçtürk et al, 2023 ), leading to abnormal plant growth and metabolism and ultimately mortality ( Mohammadhossein et al, 2019 ; Li et al, 2023 ). Therefore, reducing Cd concentrations in agricultural soils is crucial for sustainable agriculture and human health.…”