scholarly journals Autophagy mediates bronchial cell malignant transformation induced by chronic arsenic exposure via MEK/ERK1/2 pathway

2020 ◽  
Vol 332 ◽  
pp. 155-163 ◽  
Author(s):  
Linqing Wu ◽  
Zengbin Wang ◽  
Xiaotong Li ◽  
Xiaoli He ◽  
Yanfei Han ◽  
...  
Author(s):  
Mayukh Banerjee ◽  
Ana Ferragut Cardoso ◽  
Laila Al-Eryani ◽  
Jianmin Pan ◽  
Theodore S. Kalbfleisch ◽  
...  

AbstractChronic arsenic exposure causes skin cancer, although the underlying molecular mechanisms are not well defined. Altered microRNA and mRNA expression likely play a pivotal role in carcinogenesis. Changes in genome-wide differential expression of miRNA and mRNA at 3 strategic time points upon chronic sodium arsenite (As3+) exposure were investigated in a well-validated HaCaT cell line model of arsenic-induced cutaneous squamous cell carcinoma (cSCC). Quadruplicate independent HaCaT cell cultures were exposed to 0 or 100 nM As3+ for up to 28-weeks (wk). Cell growth was monitored throughout the course of exposure and epithelial-mesenchymal transition (EMT) was examined employing immunoblot. Differentially expressed miRNA and mRNA profiles were generated at 7, 19, and 28-wk by RNA-seq, followed by identification of differentially expressed mRNA targets of differentially expressed miRNAs through expression pairing at each time point. Pathway analyses were performed for total differentially expressed mRNAs and for the miRNA targeted mRNAs at each time point. RNA-seq predictions were validated by immunoblot of selected target proteins. While the As3+-exposed cells grew slower initially, growth was equal to that of unexposed cells by 19-wk (transformation initiation), and exposed cells subsequently grew faster than passage-matched unexposed cells. As3+-exposed cells had undergone EMT at 28-wk. Pathway analyses demonstrate dysregulation of carcinogenesis-related pathways and networks in a complex coordinated manner at each time point. Immunoblot data largely corroborate RNA-seq predictions in the endoplasmic reticulum stress (ER stress) pathway. This study provides a detailed molecular picture of changes occurring during the arsenic-induced transformation of human keratinocytes.


2006 ◽  
Vol 101 (2) ◽  
pp. 213-220 ◽  
Author(s):  
Blakely M. Adair ◽  
Edward E. Hudgens ◽  
Michael T. Schmitt ◽  
Rebecca L. Calderon ◽  
David J. Thomas

1994 ◽  
Vol 16 (2) ◽  
pp. 184-209 ◽  
Author(s):  
Robert R. Engel ◽  
Claudia Hopenhayn-Rich ◽  
Olivier Receveur ◽  
Allan H. Smith

2020 ◽  
Vol 318 (5) ◽  
pp. E667-E677
Author(s):  
Felicia Castriota ◽  
Peter-James H. Zushin ◽  
Sylvia S. Sanchez ◽  
Rachael V. Phillips ◽  
Alan Hubbard ◽  
...  

The global prevalence of type 2 diabetes (T2D) has doubled since 1980. Human epidemiological studies support arsenic exposure as a risk factor for T2D, although the precise mechanism is unclear. We hypothesized that chronic arsenic ingestion alters glucose homeostasis by impairing adaptive thermogenesis, i.e., body heat production in cold environments. Arsenic is a pervasive environmental contaminant, with more than 200 million people worldwide currently exposed to arsenic-contaminated drinking water. Male C57BL/6J mice exposed to sodium arsenite in drinking water at 300 μg/L for 9 wk experienced significantly decreased metabolic heat production when acclimated to chronic cold tolerance testing, as evidenced by indirect calorimetry, despite no change in physical activity. Arsenic exposure increased total fat mass and subcutaneous inguinal white adipose tissue (iWAT) mass. RNA sequencing analysis of iWAT indicated that arsenic dysregulated mitochondrial processes, including fatty acid metabolism. Western blotting in WAT confirmed that arsenic significantly decreased TOMM20, a correlate of mitochondrial abundance; PGC1A, a master regulator of mitochondrial biogenesis; and, CPT1B, the rate-limiting step of fatty acid oxidation (FAO). Our findings show that chronic arsenic exposure impacts the mitochondrial proteins of thermogenic tissues involved in energy expenditure and substrate regulation, providing novel mechanistic evidence for arsenic’s role in T2D development.


2018 ◽  
Vol 37 (1) ◽  
pp. 5-12 ◽  
Author(s):  
Mst Karimon Nesha ◽  
Md Nazrul Islam ◽  
Nira Ferdous ◽  
Fahid Bin Nazrul ◽  
Johannes J Rasker

The well-documented fact that chronic arsenic exposure can lead to skin lesions, atherosclerotic diseases and cancers. The findings of association between arsenic exposure and diabetes mellitus indicate additional risk to human health. The aim of this study was to observe the association of chronic arsenic exposure from drinking water and risk of development of type 2 diabetes mellitus. To this end, a cross-sectional study was conducted in Comilla district of Bangladesh where ground water is heavily contaminated with arsenic. The individuals unexposed to arsenic were recruited from the Jhenaidah district. People with arsenic-related skin lesions were defined as subjects exposed to arsenic. Diabetes was defined if fasting blood glucose (FBG)>6.1 mmol/L following World Health Organization (WHO) guidelines. The common odds ratio for diabetes mellitus among subjects exposed to arsenic was 3.5 (95% confidence interval 1.1-10.9). After adjustment for age, sex and BMI, the Mantel-Haenszel weighted prevalence ratio was 3.5 (95% CI: 1.1-11.1); 3.7 (95% CI: 1.1-11.8) and 4.4 (95% CI: 1.1-17.2) respectively. The indicated relationships were significant (P<0.05). The observations suggested, chronic arsenic exposure through drinking water may be a risk factor of type 2 diabetes mellitus. J Bangladesh Coll Phys Surg 2019; 37(1): 5-12


2020 ◽  
Vol 402 ◽  
pp. 115138
Author(s):  
Cody J. Schmidlin ◽  
Tao Zeng ◽  
Pengfei Liu ◽  
Yongyi Wei ◽  
Matthew Dodson ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Yajia Li ◽  
Danrong Jing ◽  
Yi Xiao ◽  
Xiaoyan Huang ◽  
Minxue Shen

Purpose. Previous studies confirmed that chronic arsenic exposure could lead to pigmentary changes and hyperkeratosis. However, skin health-related quality of life (HRQoL) among people under lifetime arsenic exposure remains underappreciated. Our study is aimed at investigating several patient-reported outcomes in a population under chronic arsenic exposure. Patients and Methods. A cross-sectional study was conducted in communities in Shimen, China. Dermatologists performed skin examinations for participants. Patient-reported outcomes (PROs) included HRQoL, itch, sleep quality, and symptoms of anxiety and depression. The Dermatology Life Quality Index (DLQI) was used to measure skin HRQoL. The numerical rating scale (NRS) was used to measure the intensity of itching. Sleep disturbance was measured by Pittsburgh Sleep Quality Index (PSQI). Anxiety and depression were measured by two-item Generalized Anxiety Disorder (GAD-2) and Patient Health Questionnaire (PHQ-2), respectively. Results. A total of 464 participants suffering from arsenic-related skin lesions finished the assessment of DLQI. Pigmentary changes and arsenical keratosis were not associated with the patient-reported outcomes except PHQ-2. Hair arsenic exceeding 1 μg/g was associated with higher itch NRS and DLQI (P<0.05). Itch NRS (adjusted β=0.80, 95% CI: 0.70–0.90, P<0.01) and hair arsenic concentration (adjusted β=0.12, 95% CI: 0.01–0.24, P<0.05) were independently associated with the DLQI. Conclusion. HRQoL, sleep quality, and mental wellbeing are impaired in residents under chronic arsenic exposure. Itching and hair arsenic are independent risk factors for impaired HRQoL.


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