Document Detail

Cell death induced by zinc and cadmium is mediated by clusterin in cultured mouse seminiferous tubules.
MedLine Citation:
PMID:  19288494     Owner:  NLM     Status:  MEDLINE    
Sertoli cells, lining the walls of the seminiferous tubules, are in close contact with and regulate all aspects of the development of the germ cells. Clusterin, is a glycoprotein produced abundantly by Sertoli cells, and associated with either apoptosis or cell survival. Zinc is present in high concentrations in the testis and required for sperm development by an as yet unknown mechanism. Permeation of zinc into cells via voltage-gated calcium channels (VGCCs), however, is suggested to induce cell death. We examined the possibility that Zn(2+) acts via clusterin to regulate germ cell survival. Employing an ex vivo model of mouse testis, we have assessed the role of permeation of heavy metal ions on clusterin production and secretion. Up-regulation of clusterin expression and its secretion was observed after a short exposure to zinc or to cadmium under depolarizing conditions. Expression of zinc transporter-1 (ZnT-1), previously shown to regulate Zn(2+) influx, increased following prolonged application of zinc or cadmium to the explants and prevented clusterin up-regulation by subsequent exposure to these ions. Inhibition of the MAPK and PI3K pathways reduced the up-regulation of clusterin following the intracellular rise of Zn(2+) or Cd(2+). Neutralization of secreted clusterin by an antibody or attenuation of clusterin up-regulation by inhibition of Zn(2+) permeation via the LTCC, reduced cell death in cultured seminiferous tubule cells. Taken together, our results indicate that Zn(2+) and Cd(2+) influx induce expression and secretion of clusterin, thereby linking metal homeostasis and germ cell fate.
Tehila Kaisman-Elbaz; Israel Sekler; Daniel Fishman; Nataly Karol; Michal Forberg; Nicole Kahn; Michal Hershfinkel; William F Silverman
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  220     ISSN:  1097-4652     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-05-04     Completed Date:  2009-05-14     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  222-9     Citation Subset:  IM    
Department of Morphology, Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer Sheva, Israel.
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MeSH Terms
1-Phosphatidylinositol 3-Kinase / antagonists & inhibitors,  metabolism
Cadmium / metabolism,  pharmacology*
Calcium Channel Blockers / pharmacology
Calcium Channels, L-Type / metabolism
Cation Transport Proteins / metabolism
Cell Death / drug effects
Cell Membrane Permeability
Clusterin / metabolism*
Enzyme Activation
Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors,  metabolism
Protein Kinase Inhibitors / pharmacology
Seminiferous Tubules / drug effects*,  metabolism,  pathology
Signal Transduction / drug effects
Time Factors
Tissue Culture Techniques
Zinc / metabolism,  pharmacology*
Reg. No./Substance:
0/Calcium Channel Blockers; 0/Calcium Channels, L-Type; 0/Cation Transport Proteins; 0/Clu protein, mouse; 0/Clusterin; 0/Protein Kinase Inhibitors; 0/Slc30a1 protein, mouse; 7440-43-9/Cadmium; 7440-66-6/Zinc; EC 3-Kinase; EC Protein Kinase Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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