Heptachlor and the mitogen-activated protein kinase module in human lymphocytes

The organochlorine pesticide heptachlor constitutes a potential health hazard because of its persistence in nature, its reported contamination in food and milk, and its possible carcinogenic effects. As a tumor promoter, heptachlor induces human myeloblastic leukemia cells to differentiate, and also...

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Bibliographic Details
Published in:Toxicology (Amsterdam) 1998-06, Vol.128 (1), p.17-23
Main Authors: Chuang, Linda F, Chuang, Ronald Y
Format: Article
Language:English
Subjects:
B-Lymphocytes - drug effects
B-Lymphocytes - enzymology
Biological and medical sciences
Blotting, Western
Calcium-Calmodulin-Dependent Protein Kinases - metabolism
Cell Division - drug effects
Cells, Cultured
Electrophoresis, Polyacrylamide Gel
Heptachlor
Heptachlor - toxicity
Human immune cells
Humans
Hybrid Cells
Immunoblotting
Insecticide
Insecticides - toxicity
Lymphocytes - drug effects
Lymphocytes - enzymology
MAP kinase module
Medical sciences
Pesticides, fertilizers and other agrochemicals toxicology
T-Lymphocytes - drug effects
T-Lymphocytes - enzymology
Toxicology
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Summary:The organochlorine pesticide heptachlor constitutes a potential health hazard because of its persistence in nature, its reported contamination in food and milk, and its possible carcinogenic effects. As a tumor promoter, heptachlor induces human myeloblastic leukemia cells to differentiate, and also down-regulates the tumor suppresser gene p53 in human immune cells. In this study, the heptachlor signaling pathway in human lymphocytes was studied. Addition of heptachlor to human CEM x174 lymphocytic cells reduced the cellular levels of MAP kinase (MAPK, mitogen-activated protein kinase) cascade proteins, including ERK1 (a 44-kDa MAPK), ERK2 (a 42-kDa MAPK), a 85-kDa and a 54-kDa MAP kinase, MEK1 (a 45-kDa ERK kinase) and MEKK (a 78-kDa MEK kinase). However, heptachlor treatment caused a marked increase in the expression of the activated (Thr- and Tyr-dually phosphorylated) ERK1 and ERK2 in the cells. These studies indicate that mitogen-activated protein kinases are important intermediates in the signal transduction pathway of immune cells upon heptachlor exposure, and the observation of stimulation of activated MAP kinases without a simultaneous accumulation of basal enzymes may suggest the involvement of a negative feedback control mechanism in the pathway.
ISSN:0300-483X
1879-3185
DOI:10.1016/S0300-483X(98)00042-0