A Clinical Perspective on Arsenic Exposure and Development of Atherosclerotic Cardiovascular Disease

Kaur, Gurleen; Desai, Karan; Chang, Isabella Y; Newman, Jonathan; Mathew, Roy; Bangalore, Sripal; Venditti, Ferdinand J.; Sidhu, Mandeep S.

doi:10.1007/s10557-021-07313-9

Cited by 1 publication

(1 citation statement)

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“…As a known group I human carcinogen, it is considered to be a major causative factor in some human cancers, such as skin, lung, and bladder cancer. It is also suggested to cause a widespread range of acute and chronic health effects, including cardiovascular, neurological and renal disorders, and diabetes (Farkhondeh et al 2019 ; Garza-Lombo et al 2019 ; Kaur et al 2022 ; Zhang et al 2019 ). What’s more, studies now believe that diseases mentioned above may be related to aberrant immune function in the human body, making the immunotoxicity of As one of the hot research topics.…”

Section: Introductionmentioning

confidence: 99%

TFEB and TFE3 cooperate in regulating inorganic arsenic-induced autophagy-lysosome impairment and immuno-dysfunction in primary dendritic cells

Xu,

Peng,

Yao

et al. 2024

Cell Biol Toxicol

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Arsenic (As) is a prevalent and hazardous environmental toxicant associated with cancer and various health problems, which has been shown suppressive effects on dendritic cells (DCs). Autophagy is essential for the innate and adaptive immune responses of DCs, and the transcription factors TFEB and TFE3 are key regulators of autophagic and lysosomal target genes. However, the detrimental alterations of the autophagy-lysosome pathway in As-exposed DCs and the possible coordinating roles of TFEB and TFE3 in the immune dysfunction of this cell are less understood. In this paper, we found that As exposure significantly impaired lysosomal number, lysosomal acidic environment, and lysosomal membrane permeabilization, which might lead to blocked autophagic flux in cultured DCs. Furthermore, our results confirmed that TFEB or TFE3 knockdown exacerbated the disorders of lysosome and the blockade of autophagic flux in As-exposed DCs, and also enhanced the inhibitory expression of co-stimulatory molecules Cd80 and Cd83; adhesion molecule Icam1; cytokines TNF-α, IL-1β, and IL-6; chemokine receptor Ccr7; and antigen-presenting molecules MHC II and MHC I. By contrast, overexpression of TFEB or TFE3 partially alleviated the above-mentioned impairment of DCs by inorganic As exposure. In conclusion, these findings reveal a previously unappreciated inhibition of lysosome-mediated degradation and damage of lysosomal membrane integrity leading to dysregulated autophagy and impaired immune functions of DCs by arsenicals, and also suggest TFEB and TFE3 as potential therapeutic targets for ameliorating As toxicity. Graphical abstract

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