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Proteomic responses of BEAS-2B cells to nontoxic and toxic chromium: Protein indicators of cytotoxicity conversion.

Abstract：

:Hexavalent chromium (Cr (VI)) is an environmental human carcinogen which primarily targets lungs. Among a variety of toxic mechanisms, disruption of biological pathways via translational and post-translational modifications represents a key mechanism through which Cr (VI) induces cytotoxicity and carcinogenesis. To identify those disruptions which are altered in response to cytotoxic Cr (VI) exposures, we measured and compared cytotoxicity and changes in expression and phosphorylation status of 15 critical biochemical pathway regulators in human BEAS-2B cells exposed for 48h to a non-toxic concentration (0.3μM) and a toxic concentration (1.8μM) of Cr (VI) by ELISA techniques. In addition, 43 functional proteins which may be altered in response to pathway signaling changes were identified using two dimensional electrophoresis (2-DE) and mass spectrometry. The proteins and fold changes observed in cells exposed to the non-toxic dose of Cr (VI) (0.3μM) were not necessarily the same as those found in the toxic one (1.8μM). A subset of signaling proteins that were correlated with the cytotoxic responses of human BEAS-2B cells to Cr (VI) treatments were identified. These proteins include regulators of glycolysis, glycogen synthase kinase 3 beta (GSK3β) and phosphoprotein 70 ribosomal protein s6 kinase (p70S6K), a signaling protein associated with oxidative stress and inflammation responses, JNK and metal regulatory transcription factor 1 (MTF-1), and a source of ubiquitin for signaling targeted protein degradation, polyubiquitin C (UBC). In addition, two dimensional gel electrophoresis (2-DE) was applied to identify key alterations in biochemical pathways differentiating between cytotoxic and non-cytotoxic exposures to Cr (VI), including glycolysis and gluconeogenesis, protein degradation, inflammation, and oxidative stress.

journal_name

Toxicol Lett

journal_title

Toxicology letters

authors

Bruno M,Ross J,Ge Y

doi

10.1016/j.toxlet.2016.08.025

subject

Has Abstract

pub_date

2016-12-15 00:00:00

pages

59-70

eissn

0378-4274

issn

1879-3169

pii

S0378-4274(16)33128-9

journal_volume

264

pub_type

杂志文章

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Proteomic responses of BEAS-2B cells to nontoxic and toxic chromium: Protein indicators of cytotoxicity conversion.