Skip Navigation



ToxSci Advance Access published online on June 19, 2009
Toxicological Sciences, doi:10.1093/toxsci/kfp132
This Article
Right arrow Advance Access manuscript (PDF)
Right arrow All Versions of this Article:
111/1/100    most recent
kfp132v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Zuo, P.
Right arrow Articles by Waalkes, M. P.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zuo, P.
Right arrow Articles by Waalkes, M. P.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Published by Oxford University Press 2009.

Potential Role of {alpha}-Synuclein and Metallothionein in Lead-Induced Inclusion Body Formation

Peijun Zuo*, Wei Qu*, Ryan N. Cooper*, Robert A. Goyer*, Bhalchandra A. Diwan{dagger} and Michael P. Waalkes*,1

* Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at the National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA {dagger} Basic Research Program, SAIC-Frederick, Inc., NCI at Frederick, MD, USA, 21702

1 Address for correspondence: Dr. Michael P. Waalkes, Chief, Inorganic Carcinogenesis Section, NCI at NIEHS, PO Box 12233, Mail Drop F0-09, 111 Alexander Drive, Research Triangle Park, NC 27709, USA. Phone (919)-541-2328; fax (919)-541-3970; e-mail: waalkes{at}niehs.nih.gov

Received April 7, 2009; revision received June 2, 2009; accepted June 4, 2009


  Abstract

Lead (Pb) produces aggresome-like inclusion bodies (IBs) in target cells as a toxic response. Our prior work shows metallothionein (MT) is required for this process. We used MT-I/II double knock-out (MT-null) and parental wild type (WT) cell lines to further explore the formation process of Pb induced IBs. Unlike WT cells, MT-null cells did not form IBs after Pb exposure. Western blot of cytosol showed soluble MT protein in WT cells was lost during Pb exposure as IBs formed. Transfection of MT-I into MT-null cells allowed IBs formation after Pb exposure. Considering Pb-induced IBs may be like disease-related aggresomes, which often contain {alpha}-synuclein (Scna), we investigated Scna expression in cells capable (WT) and incapable (MT-null) of producing IBs after Pb exposure. Scna protein showed poor basal expression in MT-null cells. Pb exposure increased Scna expression only in WT cells. MT-transfection increased Scna transcript to WT levels. In WT or MT-transfected MT-null cells, Pb-induced Scna expression rapidly increased and then decreased over 48 h as Pb-induced IBs were formed. A direct interaction between Scna and MT was confirmed ex vivo by antibody pulldown assay where the proteins co-precipitated with an antibody to MT. Pb exposure caused increased co-localization of MT and Scna proteins with time only in WT cells. In WT mice after chronic Pb exposure Scna was localized in renal cells containing forming IBs while MT-null mice did not form IBs. Thus, Scna could be component of Pb-induced IBs and, with MT, may play a role in IBs formation.

Key Words: Lead; inclusion bodies; {alpha}-synuclein; metallothionein; MT-null.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.