Skip Navigation



Journal of Biochemistry Advance Access published online on December 19, 2006
Journal of Biochemistry, doi:10.1093/jb/mvm030
This Article
Right arrow Advance Access manuscript (PDF)
Right arrow All Versions of this Article:
141/2/239    most recent
mvm030v1
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 arrow Request Permissions
Google Scholar
Right arrow Articles by Michihara, A.
Right arrow Articles by Tsuji, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Michihara, A.
Right arrow Articles by Tsuji, H.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2006 The Japanese Biochemical Society

Decrease of cholesterol in mouse melanoma causes secretion of lysosomal enzymes.

Akihiro Michihara*, Ken Toda, Michihisa Suenobu, Kenji Akasaki and Hiroshi Tsuji

Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Fukuyama, Hiroshima 729-0292, Japan

*To whom correspondence should be addressed. E-mail: mitihara{at}fupharm.fukuyama-u.ac.jp

Received February 21, 2006; Accepted December 8, 2006


  Abstract

We examined the change in the subcellular distribution of a lysosomal enzyme, ß-glucuronidase (ß-G), caused by decreased cholesterol levels in mouse melanoma cells using a HMG-CoA reductase inhibitor, lovastatin, and lipoprotein-deficient serum (LDS). There was a decrease in the cholesterol content of the cells and increased secretion of the mature form of ß-G located in lysosomes, as documented by Percoll density gradient fractionation, digitonin permeabilization, and immunoprecipitation. Furthermore, another lysosomal enzyme, cathepsin H, was found to be released in the medium from cells treated with lovastatin. Both the precursor and mature forms of cathepsin H were detected in the medium of treated cells. Next, when cells were treated with LDS without lovastatin, concomitantly with the decrease in the levels of cholesterol and ß-G activity in the cells, ß-G activity in the medium increased. Also, the ratio of ß-G (3.2-fold) released in the medium from cells treated with D-MEM containing lovastatin and LDS was higher than that (2.3-fold) on treatment with D-MEM containing LDS without lovastatin. From these results, it was suggested that the exocytosis of mature enzymes from lysosomes into the medium or mis-sorting of the lysosomal precursor forms to the medium was caused by the lovastatin- and/or LDS-induced decrease in the cholesterol content of the cells, although the mechanism of secretion by lysosomal enzymes differed somewhat.

Key Words: mouse, melanoma, lysosome, exocytosis, mis-sorting, ß-glucuronidase, cathepsin H


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.