JCB logo
Quantitative Colocalization Analysis Software
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online
doi:10.1083/jcb.200712156
The Journal of Cell Biology, Vol. 181, No. 7, 1065-1072
The Rockefeller University Press, 0021-9525 $30.00
© Hashimoto et al.
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 3701K)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Related biobytes podcast
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hashimoto, D.
Right arrow Articles by Yamamura, K.-i.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hashimoto, D.
Right arrow Articles by Yamamura, K.-i.
Right arrowPubmed/NCBI databases
*Gene*GEO Profiles
*HomoloGene*UniGene
*Compound via MeSH
*Substance via MeSH
Related Collections
Right arrowRelated In this Issue article
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Report

Involvement of autophagy in trypsinogen activation within the pancreatic acinar cells



Daisuke Hashimoto1,2, Masaki Ohmuraya1,2, Masahiko Hirota2, Akitsugu Yamamoto3, Koichi Suyama1,2, Satoshi Ida1,2, Yuushi Okumura4,5, Etsuhisa Takahashi5, Hiroshi Kido5, Kimi Araki1, Hideo Baba2, Noboru Mizushima6,7, and Ken-ichi Yamamura1

1 Division of Developmental Genetics, Institute of Molecular Embryology and Genetics, and 2 Department of Gastroenterological Surgery, Kumamoto University, Kumamoto 860-0811, Japan
3 Department of Bioscience, Nagahama Institute of Bioscience and Technology, Nagahama, Shiga 526-0829, Japan
4 Department of Nutritional Physiology, Institute of Health Biosciences, and 5 Division of Enzyme Chemistry, Institute for Enzyme Research, University of Tokushima Graduate School, Tokushima 770-8503, Japan
6 Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8519, Japan
7 Solution-Oriented Research for Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan

Correspondence to Ken-ichi Yamamura: yamamura{at}gpo.kumamoto-u.ac.jp

Autophagy is mostly a nonselective bulk degradation system within cells. Recent reports indicate that autophagy can act both as a protector and killer of the cell depending on the stage of the disease or the surrounding cellular environment (for review see Cuervo, A.M. 2004. Trends Cell Biol. 14:70–77). We found that cytoplasmic vacuoles induced in pancreatic acinar cells by experimental pancreatitis were autophagic in origin, as demonstrated by microtubule-associated protein 1 light chain 3 expression and electron microscopy experiments. To analyze the role of macroautophagy in acute pancreatitis, we produced conditional knockout mice lacking the autophagy-related 5 gene in acinar cells. Acute pancreatitis was not observed, except for very mild edema in a restricted area, in conditional knockout mice. Unexpectedly, trypsinogen activation was greatly reduced in the absence of autophagy. These results suggest that autophagy exerts devastating effects in pancreatic acinar cells by activation of trypsinogen to trypsin in the early stage of acute pancreatitis through delivering trypsinogen to the lysosome.

D. Hashimoto and M. Ohmuraya contributed equally to this paper.

Abbreviations used in this paper: Atg, autophagy related; CCK, cholecystokinin; H&E, hematoxylin and eosin; LC3, light chain 3; TAP, trypsinogen activation peptide.

© 2008 Hashimoto et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?

Related In this Issue article

Cellular self-eating promotes pancreatitis
Mitch Leslie
J. Cell Biol. 2008 181: 1042. [Full Text] [PDF]



This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents