| Cell death induced by zinc and cadmium is mediated by clusterin in cultured mouse seminiferous tubules. | |
| | |
MedLine Citation:
|
PMID: 19288494 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
Tehila Kaisman-Elbaz; Israel Sekler; Daniel Fishman; Nataly Karol; Michal Forberg; Nicole Kahn; Michal Hershfinkel; William F Silverman |
Related Documents
:
|
1426354 - Assessment of testicular cytology by fine needle aspiration as a diagnostic parameter i... 6501084 - Fetal irradiation increases androgen production by dispersed leydig cells of the rat. 11585094 - Alternative cell lines for the propagation of lumpy skin disease virus. 3009604 - Immunohistochemical localization of two angiotensin i-converting isoenzymes in the repr... 22552784 - The flavonoid resveratrol suppresses growth of human malignant pleural mesothelioma cel... 1924254 - A simple and efficient method for purifying and quantifying schizonts from theileria pa... |
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 |
Affiliation:
|
Department of Morphology, Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer Sheva, Israel. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
1-Phosphatidylinositol 3-Kinase
/
antagonists & inhibitors,
metabolism Animals 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 Male Mice 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 Up-Regulation Zinc / metabolism, pharmacology* |
| Chemical | |
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 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.12.2/Mitogen-Activated Protein Kinase Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Role of RAF/MEK/ERK pathway, p-STAT-3 and Mcl-1 in sorafenib activity in human pancreatic cancer cel...
Next Document: Defective co-activator recruitment in osteoclasts from microphthalmia-oak ridge mutant mice.