Antimony exposure promotes bladder tumor cell growth by inhibiting PINK1-Parkin-mediated mitophagy

Lou, Yantao; Ma, C.; Liu, Zhifei; Shi, Jianxi; Zheng, Guangzhe; Zhang, Chang-wen

doi:10.1016/j.ecoenv.2021.112420

Cited by 20 publications

(7 citation statements)

References 37 publications

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“…Furthermore, Sb impairs glutathione peroxidase activity, reducing free glutathione levels and increasing cellular vulnerability to oxidative stress (44). Even at low doses, Sb significantly impacts mitochondrial function, decreasing mitochondrial membrane potential, respiratory enzyme complex activity (I/II/III/IV), ATP/ADP ratio, and ATP concentration (45). Sb exposure also inhibited intracellular pyruvate dehydrogenase activity, causing an increase in anaerobic glycolysis and resulting in a decrease in intracellular ATP levels.…”

Section: Discussionmentioning

confidence: 99%

Sex-specific associations between nine metal mixtures in urine and urine flow rate in US adults: NHANES 2009–2018

Zhang

Tang

Zhou

2023

Front. Public Health

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BackgroundThe urinary system serves as a crucial pathway for eliminating metallic substances from the body, making it susceptible to the effects of metal exposure. However, limited research has explored the association between metal mixtures and bladder function. This study aims to investigate the relationship between urinary metal mixtures (specifically barium, cadmium, cobalt, cesium, molybdenum, lead, antimony, thallium, and tungsten) and urine flow rate (UFR) in the general population, utilizing multiple mixture analysis models.MethodsThis study utilizes data obtained from the National Health and Nutrition Examination Survey. After adjusting for relevant covariates, we assessed the correlations between metal mixtures and UFR using three distinct analysis models: weighted quantile sum (WQS), quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR). Additionally, a gender-stratified analysis was conducted. Finally, we also performed sensitivity analyses.ResultsA total of 7,733 subjects were included in this study, with 49% being male. The WQS regression model, when fitted in the positive direction, did not yield any significant correlations in the overall population or in the male and female subgroups. However, when analyzed in the negative direction, the WQS index exhibited a negative correlation with UFR in the overall group (β = −0.078; 95% CI: −0.111, −0.045). Additionally, a significant negative correlation between the WQS index and UFR was observed in the female group (β = −0.108; 95% CI: −0.158, −0.059), while no significant correlation was found in the male group. The results obtained from the qgcomp regression model were consistent with those of the WQS regression model. Similarly, the BKMR regression model revealed a significant negative correlation trend between metal mixtures and UFR, with cadmium and antimony potentially playing key roles.ConclusionOur study revealed a significant negative correlation between urinary metal mixture exposure and mean UFR in US adults, with notable gender differences. Specifically, higher urinary levels of cadmium and antimony were identified as potential key factors contributing to the decrease in mean UFR. These findings significantly contribute to the existing knowledge on the impact of metal mixtures on bladder function and provide valuable insights for safeguarding bladder health and preventing impaired bladder function.

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Section: Discussionmentioning

confidence: 99%

Sex-specific associations between nine metal mixtures in urine and urine flow rate in US adults: NHANES 2009–2018

Zhang

Tang

Zhou

2023

Front. Public Health

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“…We have found that the m.15059G>A mutation can negatively affect mitophagy activation in monocytes, leading to defective mitophagy. It is known that defective mitophagy, caused by the influence of certain agents on cells or mutations in nuclear genes, is accompanied by reduced activity of complex III of the mitochondrial respiratory chain 40,41 . We hypothesize that in our study, an opposite effect was observed, where the impaired activity of complex III contributed to the reduction of mitophagy activity in cells.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial genome editing: a possible interplay of atherosclerosis-associated mutation m.15059G>A with defective mitophagy

Khotina

Kalmykov

Zhuravlev

et al. 2023

Preprint

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Objective: It was assumed that the cause of chronic inflammation in atherosclerosis is a disturbance of the innate immunity response, caused, among other factors, by mitochondrial dysfunctions. It was also suggested that mitochondrial dysfunction may be caused by heteroplasmic mutations in mitochondrial DNA. The aim of this study was to evaluate the effect of the mitochondrial nonsense mutation m.15059G>A on cellular functions in atherosclerosis: lipoidosis, pro-inflammatory response, and mitophagy. Approach and Results: The human monocytic cell line THP-1 and cytoplasmic hybrid cell line TC-HSMAM1 were used. An original approach based on the CRISPR/Cas9 system was developed and used for the elimination of mtDNA copies carrying the m.15059G>A mutation in the MT-CYB gene. Using this approach, the Cas9-TC-HSMAM1 cells with an eliminated m.15059G>A mutation was obtained. The gene expression levels of genes encoding enzymes related to cholesterol metabolism were analyzed by quantitative RT-PCR. The evaluation of pro-inflammatory cytokine secretion was assessed using ELISA. Mitophagy in cells was detected using confocal microscopy. In contrast to intact TC-HSMAM1 cybrids, in Cas9-TC-HSMAM1 cells, incubation with atherogenic LDL led to a decrease in the expression of the gene encoding fatty acid synthase (FASN). It was found that TC-HSMAM1 cybrids are characterized by defective mitophagy and are also unable to reduce the production of pro-inflammatory cytokines (to form immune tolerance) in response to repeated LPS stimulation. Elimination of mtDNA carrying the m.15059G>A mutation led to the restoration of immune tolerance and activation of mitophagy in the studied cells. Conclusion: The m.15059G>A mutation was found to be associated with defective mitophagy, immune tolerance, and impaired metabolism of intracellular lipids due to upregulation of the FASN. Thus, this mutation may play an important role in atherogenesis due to its contribution to the chronification of inflammation, which aggravates the progression of atherosclerosis.

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“… 30 Additionally, one of the heavier pnictogens, antimony, contributes to cancer by inhibiting the PINK1/Parkin pathway‐controlled process of mitophagy. 31 These observations indicate that the function of PINK1 in regulating mitophagy might be a double‐edged sword for cancer. Further detailed studies are needed to uncover the exact potential clinical significance of PINK1.…”

Section: Pink1 Regulation Of Mitophagy In Cancermentioning

confidence: 98%

“…Furthermore, studies have demonstrated that in neuroblastoma cells, manganese (Mn), an environmental risk factor of PD that is thought to induce manganism, protects dopaminergic neuronal cells from death by triggering PINK1/Parkin‐mediated mitophagy 30 . Additionally, one of the heavier pnictogens, antimony, contributes to cancer by inhibiting the PINK1/Parkin pathway‐controlled process of mitophagy 31 . These observations indicate that the function of PINK1 in regulating mitophagy might be a double‐edged sword for cancer.…”

Section: Pink1 Regulation Of Mitophagy In Cancermentioning

confidence: 99%

The emerging multifaceted role of PINK1 in cancer biology

et al. 2022

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For its various important functions in cells, phosphatase and tensin homolog‐induced kinase 1 (PINK1) has drawn considerable attention for the role it plays in early‐onset Parkinson's disease. In recent years, emerging evidence has supported the hypothesis that PINK1 plays a part in regulating many physiological and pathophysiological processes in cancer cells, including cytoplasmic homeostasis, cell survival, and cell death. According to the findings of these studies, PINK1 can function as a tumor promoter or suppressor, showing a duality that is dependent on the context. In this study we review the mechanistic characters relating to PINK1 based on available published data from peer‐reviewed articles, The Cancer Genome Atlas data mining, and cell‐based assays. This mini review focuses on some of the interplays between PINK1 and the context and recent developments in the field, including its growing involvement in mitophagy and its nonmitophagy organelles‐related function. This review aims to help readers better grasp how PINK1 is functioning in cell physiological and pathophysiological processes, especially in cancer biology.

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Antimony exposure promotes bladder tumor cell growth by inhibiting PINK1-Parkin-mediated mitophagy

Cited by 20 publications

References 37 publications

Sex-specific associations between nine metal mixtures in urine and urine flow rate in US adults: NHANES 2009–2018

Sex-specific associations between nine metal mixtures in urine and urine flow rate in US adults: NHANES 2009–2018

Mitochondrial genome editing: a possible interplay of atherosclerosis-associated mutation m.15059G>A with defective mitophagy

The emerging multifaceted role of PINK1 in cancer biology

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