Involvement of Autophagy in Trypsinogen Activation Within the Pancreatic Acinar Cells

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2008 Jul 2

PMID 18591426

Citations 108

Authors

Daisuke Hashimoto

Masaki Ohmuraya

Masahiko Hirota

Akitsugu Yamamoto

Koichi Suyama

Satoshi Ida

Yuushi Okumura

Etsuhisa Takahashi

Hiroshi Kido

Kimi Araki

Hideo Baba

Noboru Mizushima

Ken-Ichi Yamamura

Affiliations

Soon will be listed here.

Abstract

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.

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