Neuregulin 1-?eta Cytoprotective Role in AML 12 Mouse Hepatocytes Exposed to Pentachlorophenol

Waneene C. Dorsey, Paul B. Tchounwou and Byron D. Ford
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Waneene C. Dorsey: Molecular Toxicology Research Laboratory, Grambling State University, Grambling, LA, USA
Paul B. Tchounwou: Molecular Toxicology Research Laboratory, NIH-Center for Environmental Health, College of Science, Engineering, and Technology, Jackson State University, Jackson, MS, USA
Byron D. Ford: Department of Anatomy and Neurobiology, Morehouse School of Medicine, Atlanta, GA, USA

IJERPH, 2006, vol. 3, issue 1, 1-12

Abstract: Neuregulins are a family of growth factor domain proteins that are structurally related to the epidermal growth factor. Accumulating evidence has shown that neuregulins have cyto- and neuroprotective properties in various cell types. In particular, the neuregulin-1 ?eta (NRG1-?) isoform is well documented for its antiinflammatory properties in rat brain after acute stroke episodes. Pentachlorophenol (PCP) is an organochlorine compound that has been widely used as a biocide in several industrial, agricultural, and domestic applications. Previous investigations from our laboratory have demonstrated that PCP exerts both cytotoxic and mitogenic effects in human liver carcinoma (HepG 2 ) cells, primary catfish hepatocytes and AML 12 mouse hepatocytes. We have also shown that in HepG2 cells, PCP has the ability to induce stress genes that may play a role in the molecular events leading to toxicity and tumorigenesis. In the present study, we hypothesize that NRG1-? will exert its cytoprotective effects in PCP-treated AML 12 mouse hepatocytes by its ability to suppress the toxic effects of PCP. To test this hypothesis, we performed the MTT-cell respiration assay to assess cell viability, and Western-blot analysis to assess stress-related proteins as a consequence of PCP exposure. Data obtained from 48 h-viability studies demonstrated a biphasic response; showing a dose-dependent increase in cell viability within the range of 0 to 3.87 ?g/mL, and a gradual decrease within the concentration range of 7.75 to 31.0 ?g/mL in concomitant treatments of NRG1-?+PCP and PCP. Cell viability percentages indicated that NRG1-?+PCPtreated cells were not significantly impaired, while PCP-treated cells were appreciably affected; suggesting that NRG1-? has the ability to suppress the toxic effects of PCP. Western Blot analysis demonstrated the potential of PCP to induce oxidative stress and inflammatory response ( c-fos ), growth arrest and DNA damage (GADD153), proteotoxic effects (HSP70), cell cycle arrest as consequence of DNA damage (p53), mitogenic response (cyclin-D1), and apoptosis (caspase-3). NRG1-? exposure attenuated stress-related protein expression in PCP-treated AML 12 mouse hepatocytes. Here we provide clear evidence that NRG1-? exerts cytoprotective effects in AML 12 mouse hepatocytes exposed to PCP.

Keywords: Cytoprotection; Neuregulin1-ß; Pentachlorophenol; Cytotoxicity; Mouse Hepatocytes (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2006
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