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

This Article Full Text (PDF) 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 Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sasaki, T. Articles by Senda, M. Search for Related Content PubMed PubMed Citation Articles by Sasaki, T. Articles by Senda, M.

Distribution of Glutathione and Technetium-99m-meso-HMPAO in Normal and Diethyl Maleate-Treated Mouse Brain Mitochondria

Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Tokyo; Faculty of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan

Correspondence: For correspondence or reprints contact: Toru Sasaki, PhD, Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, 1-1 Naka-cho, Itabasahi, Tokyo 173, Japan.

ABSTRACT

The aim of this study was to explain the contribution of mitochondria to the accumulation of ^99mTc-meso-hexamethyl propyleneamine oxime (HMPAO) in the brain, after examinations were performed. Methods: We studied subcellular distribution of ^99mTc-meso-HMPAO and glutathione (GSH) in normal and diethyl maleate (DEM)-administered mice. Results: In normal brain, major radioactivity was found in the mitochondrial (49.0%) and cytosolic fractions (33.0%), while the GSH content was high in the cytosol (63.2%) and mitochondria (30.6%). The radioactivity in mitochondrial, cytosolic, microsomal and nuclear fractions was decreased in a dose-dependent manner by DEM, a GSH depleting agent, to 32.2% (mitochondrial) and 24.7% (cytosolic) of the control by a dose of 550 mg/kg. The GSH content in mitochondrial and cytosolic fractions also decreased in a dose-dependent manner on DEM treatment to 29.3% (mitochondrial) and 30.0% (cytosolic) of the control by 550 mg/kg of DEM. A good correlation was found between the uptake of ^99mTc-meso-HMPAO and GSH content in mitochondrial, cytosolic and nuclear fractions, with a correlation coefficient (r) of 0.814,0.834 and 0.784, respectively. Conclusion: Mitochondria are a major subcellular fraction for the uptake of ^99mTc-meso-HMPAO by the brain, and GSH in mitochondria contributes to the accumulation of ^99mTc-meso-HMPAO.

Key Words: subcellular distribution • glutathione • mitochondria • technetium-99m-meso-hexamethyl propyleneamine oxime • brain