Transcription Factors and Downstream Genes in Cadmium Toxicity

Tokumoto, Maki; Lee, Jin‐Yong; Satoh, Masahiko

doi:10.1248/bpb.b19-00204

Cited by 21 publications

(14 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…To date, epidemiological studies in humans and experimental studies in animals have linked increases in urinary excretion of LMW proteins such as β 2 -MG with the loss of functional PTECs and nephrons in the kidney at the advanced stage of Cd nephrotoxicity [25,26]. Most mechanistic studies on Cd cytotoxicity have focused on the molecular pathways leading to Cd-associated cell death and not on the direct effects of Cd on the endocytic uptakes of LMW proteins in living PTECs [15][16][17]. However, the effects of moderately higher, but not lethal, doses of Cd on the reabsorption efficiencies of LMW proteins by the surviving PTECs remain unclear.…”

Section: Discussionmentioning

confidence: 99%

“…The reabsorption of luminal biomolecules including β 2 -MG and MT by PTECs is mediated by megalin-dependent endocytosis at the apical membrane of PTECs [ 11 , 12 , 13 , 14 ]. However, many studies on Cd cytotoxicity have focused on the mechanisms of cell lethality, including apoptosis caused by Cd [ 15 , 16 , 17 ], and only a few studies have examined Cd’s direct effects on the efficiency of protein reabsorption by PTECs [ 18 , 19 ], especially under conditions where PTECs are surviving in the presence of Cd.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

In Vitro Evaluation of the Effects of Cadmium on Endocytic Uptakes of Proteins into Cultured Proximal Tubule Epithelial Cells

Fujishiro

Yamamoto

Otera

et al. 2020

Toxics

View full text Add to dashboard Cite

Cadmium (Cd) is an environmental pollutant known to cause dysfunctions of the tubular reabsorption of biomolecules in the kidney. Elevated levels of urinary excretion of low-molecular-weight proteins such as β2-microglobulin (β2-MG) have been used as an indicator of Cd-induced renal tubular dysfunctions. However, very few studies have examined the direct effects of Cd on the reabsorption efficiency of proteins using cultured renal cells. Here, we developed an in vitro assay system for quantifying the endocytic uptakes of fluorescent-labeled proteins by flow cytometry in S1 and S2 cells derived from mouse kidney proximal tubules. Endocytic uptakes of fluorescent-labeled albumin, transferrin, β2-MG, and metallothionein into S1 cells were confirmed by fluorescence imaging and flow cytometry. The exposure of S1 and S2 cells to Cd at 1 and 3 µM for 3 days resulted in significant decreases in the uptakes of β2-MG and metallothionein but not in those of albumin or transferrin. These results suggest that Cd affects the tubular reabsorption of low-molecular-weight proteins even at nonlethal concentrations. The in vitro assay system developed in this study to evaluate the endocytic uptakes of proteins may serve as a useful tool for detecting toxicants that cause renal tubular dysfunctions.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

In Vitro Evaluation of the Effects of Cadmium on Endocytic Uptakes of Proteins into Cultured Proximal Tubule Epithelial Cells

Fujishiro

Yamamoto

Otera

et al. 2020

Toxics

View full text Add to dashboard Cite

show abstract

“…Солі кадмію виявляють різнопланові токсичні ефекти на організм ссавців, призводять до виражених змін генної експресії та обміну речовин (Tokumoto et al, 2019). Основним механізмом пошкоджуючої дії іонів кадмію на клітини вважають оксидативний стрес, який кадмій, що не є перехідним металом, викликає опосередковано (Liu et al, 2009).…”

Section: вступunclassified

The effect of nitrogen monoxide donors on the indexes of cadmium-induced oxidative stress in different rat tissues

2020

The Journal of v. N. Karazin Kharkiv National University, Series "Biology"

View full text Add to dashboard Cite

Oxidative stress is considered to be the main mechanism of cadmium ions toxic effect on the cells and is caused by cadmium, as a non-transition metal, indirectly. Oxidative damage to cells due to the action of cadmium ions is tissue-specific and is associated with the antioxidant system inhibition, free heme accumulation and essential metals substitution in metalloproteins. Nitrogen monoxide (NO) exhibits high affinity for heme and proteins and peptides sulfhydryl groups, known to be the main molecular targets for cadmium ions. Taking all the above-mentioned into account, the aim of this work was to study the effect of NO radicals donors on the prooxidant-antioxidant state of mammalian tissues under oxidative stress caused by cadmium chloride administration in vivo. Male Wistar rats weighing 160–200 g were used in the study. CdCl2 was administered subcutaneously at a dose of 14 mg/kg body weight. The direct donor of the NO radical sodium nitroprusside (SNP, 1 mg/kg mass) and the substrate of the NO synthase reaction L-arginine (600 mg/kg mass) were administered intraperitoneally. In order to study the corrective action, donors of the NO radical were injected 0.5 h before the cadmium salt. The objects of investigation were blood plasma and liver, kidneys and spleen homogenates of rats. The cadmium chloride treatment caused a number of prooxidant-antioxidant balance disorders, most of which were revealed a day after injection. The accumulation of lipid peroxidation products was found in rat serum, liver, and spleen. The enhancement of prooxidant processes in these tissues may originate from cadmium ions and hemolysis products entry. In the antioxidant system, significant changes were observed under cadmium action only in the liver: an increase in the reduced glutathione content and SOD activity and a decrease in catalase activity. The precursor of nitric oxide L-arginine did not change the basal level of prooxidant-antioxidant parameters, and in most cases did not affect their dynamics in the organs studied after cadmium chloride administration. A direct NO donor, sodium nitroprusside, acted in liver and spleen mostly as a prooxidant. In liver, the injection of only nitroprusside, as well as the combined administration of SNP and CdCl2, led to free radical processes activation just in two hours. In spleen, the combined treatment by SNP and cadmium salt also caused an earlier development of oxidative stress, as witnessed by an increase in lipid hydroperoxides level and a decrease in reduced glutathione content. Therefore, the injection of a direct NO donor, sodium nitroprusside, and a substrate of NO synthase, L-arginine, in selected doses has insignificant corrective action on cadmium-induced oxidative stress in the liver, kidneys and spleen. However, in blood both donors of NO effectively prevented the accumulation of lipid peroxidation products under CdCl2 treatment; in addition, L-arginine significantly reduced the lactate dehydrogenase release, which may indicate blood cells and blood vessels protection from the damage caused by cadmium ions.

show abstract

“…However, the mechanism of how cadmium causes toxicity to kidneys is still unclear. Previous studies have shown that various complex cellular and molecular mechanisms are involved [5]. Among them, the classical theory holds that cadmium can produce oxidative stress and lipid peroxidation by interfering with redox reaction which can induce cell apoptosis [6].…”

Section: Introductionmentioning

confidence: 99%

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

Deng

Wang

Geng

et al. 2020

BioMed Research International

View full text Add to dashboard Cite

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.

show abstract

Transcription Factors and Downstream Genes in Cadmium Toxicity

Cited by 21 publications

References 52 publications

In Vitro Evaluation of the Effects of Cadmium on Endocytic Uptakes of Proteins into Cultured Proximal Tubule Epithelial Cells

In Vitro Evaluation of the Effects of Cadmium on Endocytic Uptakes of Proteins into Cultured Proximal Tubule Epithelial Cells

The effect of nitrogen monoxide donors on the indexes of cadmium-induced oxidative stress in different rat tissues

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

Contact Info

Product

Resources

About