HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: db06-1273v1 56/5/1316    most recent Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Zhang, B. Articles by Song, S. Search for Related Content PubMed PubMed Citation Articles by Zhang, B. Articles by Song, S. Social Bookmarking                What's this?

1-Antitrypsin Protects ß-Cells From Apoptosis

¹ Department of Pharmaceutics, University of Florida, Gainesville, Florida
² Department of Pathology, University of Florida, Gainesville, Florida
³ Department of Pediatrics, University of Florida, Gainesville, Florida

Address correspondence and reprint requests to Sihong Song, University of Florida College of Pharmacy, Department of Pharmaceutics, P.O. Box 100494 1600 SW Archer Rd., Gainsville, FL 32610. E-mail: shsong{at}ufl.edu

Abbreviations: AAT, 1-antitrypsin; APC, antigen-presenting cell; MTT, 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide; STZ, streptozotocin; TNF-, tumor necrosis factor-; TUNEL, terminal deoxynucleotidyl transferase–mediated dUTP nick-end labeling

ß-Cell apoptosis appears to represent a key event in the pathogenesis of type 1 diabetes. Previous studies have demonstrated that administration of the serine proteinase inhibitor 1-antitrypsin (AAT) prevents type 1 diabetes development in NOD mice and prolongs islet allograft survival in rodents; yet the mechanisms underlying this therapeutic benefit remain largely unclear. Herein we describe novel findings indicating that AAT significantly reduces cytokine- and streptozotocin (STZ)-induced ß-cell apoptosis. Specifically, strong antiapoptotic activities for AAT (Prolastin, human) were observed when murine insulinoma cells (MIN6) were exposed to tumor necrosis factor-. In a second model system involving STZ-induced ß-cell apoptosis, treatment of MIN6 cells with AAT similarly induced a significant increase in cellular viability and a reduction in apoptosis. Importantly, in both model systems, treatment with AAT completely abolished induced caspase-3 activity. In terms of its activities in vivo, treatment of C57BL/6 mice with AAT prevented STZ-induced diabetes and, in agreement with the in vitro analyses, supported the concept of a mechanism involving the disruption of ß-cell apoptosis. These results propose a novel biological function for this molecule and suggest it may represent an effective candidate for attempts seeking to prevent or reverse type 1 diabetes.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?