Targets for pollutants in rat and human pancreatic beta-cells: The effect of prolonged exposure to sub-lethal concentrations of hexachlorocyclohexane isomers on the expression of function- and survival-related proteins

IF 4.2 3区环境科学与生态学 Q2 ENVIRONMENTAL SCIENCES Environmental toxicology and pharmacology Pub Date : 2023-10-20 DOI:10.1016/j.etap.2023.104299

Nela Pavlíková , Jan Šrámek , Martin Jaček , Jan Kovář , Vlasta Němcová

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Abstract

Decades after most countries banned hexachlorocyclohexane, HCH isomers still pollute the environment. Many studies described HCH as a pro-diabetic factor; nevertheless, the effect of HCH isomers on pancreatic beta-cells remains unexplored. This study investigated the effects of a one-month exposure to α-HCH, β-HCH, and γ-HCH on protein expression in human (NES2Y) and rat (INS1E) pancreatic beta-cell lines. α-HCH and γ-HCH increased proinsulin and insulin levels in INS1E cells, while β-HCH showed the opposite trend. α-HCH altered the expression of PKA, ATF3, and PLIN2. β-HCH affected the expression of GLUT1, GLUT2, PKA, ATF3, p-eIF2α, ATP-CL, and PLIN2. γ-HCH altered the expression of PKA, ATF3, PLIN2, PLIN5, and IDH1. From the tested proteins, PKA, ATF3, and PLIN-2 were the most sensitive to HCH exposure and have the potential to be used as biomarkers.

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大鼠和人胰腺β细胞中污染物的靶点：长期暴露于亚致死浓度的六氯环己烷异构体对功能和生存相关蛋白表达的影响。

在大多数国家禁用六氯环己烷几十年后，六氯环己烷异构体仍然污染环境。许多研究将六氯环己烷描述为促糖尿病因素；尽管如此，六氯环己烷异构体对胰腺β细胞的影响仍未得到探索。本研究调查了接触α-六氯环己烷、β-六氯环己烷和γ-六氯环己烷一个月对人（NES2Y）和大鼠（INS1E）胰腺β细胞系蛋白质表达的影响。α-六氯环己烷和γ-六氯环己烷增加了INS1E细胞中的胰岛素原和胰岛素水平，而β-六氯环己烷则表现出相反的趋势。α-HCH改变了PKA、ATF3和PLIN2的表达。β-HCH影响GLUT1、GLUT2、PKA、ATF3、p-eIF2α、ATP-CL和PLIN2的表达。γ-HCH改变PKA、ATF3、PLIN2、PLIN5和IDH1的表达。从测试的蛋白质来看，PKA、ATF3和PLIN-2对六氯环己烷暴露最敏感，有潜力用作生物标志物。

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来源期刊

Environmental toxicology and pharmacology 医学-毒理学

CiteScore

7.00

自引率

4.70%

发文量

185

审稿时长

34 days

期刊介绍： Environmental Toxicology and Pharmacology publishes the results of studies concerning toxic and pharmacological effects of (human and veterinary) drugs and of environmental contaminants in animals and man. Areas of special interest are: molecular mechanisms of toxicity, biotransformation and toxicokinetics (including toxicokinetic modelling), molecular, biochemical and physiological mechanisms explaining differences in sensitivity between species and individuals, the characterisation of pathophysiological models and mechanisms involved in the development of effects and the identification of biological markers that can be used to study exposure and effects in man and animals. In addition to full length papers, short communications, full-length reviews and mini-reviews, Environmental Toxicology and Pharmacology will publish in depth assessments of special problem areas. The latter publications may exceed the length of a full length paper three to fourfold. A basic requirement is that the assessments are made under the auspices of international groups of leading experts in the fields concerned. The information examined may either consist of data that were already published, or of new data that were obtained within the framework of collaborative research programmes. Provision is also made for the acceptance of minireviews on (classes of) compounds, toxicities or mechanisms, debating recent advances in rapidly developing fields that fall within the scope of the journal.