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First published online March 2, 2004

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Forewarned is forearmed: getting ready for hypoxia

A brief exposure of cells or organs to hypoxia reduces the cytotoxicity of a later prolonged period of hypoxia. A better understanding of the cellular events involved in such `hypoxic preconditioning' could therefore improve the success rate of human organ transplantation. On p. 1065, Ciro Isidoro and colleagues report that in rat hepatocytes, preconditioning-induced cytoprotection involves Ca²⁺-dependent exocytosis of lysosomes. They show that hypoxic preconditioning induces the movement of endosomes and lysosomes from their perinuclear position in oxygenated hepatocytes to the plasma membrane. There, the lysosomes in particular fuse with the membrane and release their contents. Inhibition of lysosomal exocytosis by disruption of the actin cytoskeleton or by inhibition of phosphoinositide 3-kinase (PI3K) prevents cytoprotection in response to hypoxic preconditioning. Furthermore, an increase in cytosolic free Ca²⁺ concentration, which is induced by PI3K, is necessary for exocytosis of endosomal/lysosomal organelles and for cytoprotection. On the basis of these findings, the authors suggest that drugs that stimulate membrane recycling could help to protect organs destined for transplantation from hypoxia.

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Preconditioning-induced cytoprotection in hepatocytes requires Ca²⁺-dependent exocytosis of lysosomes

Rita Carini, Roberta Castino, Maria Grazia De Cesaris, Roberta Splendore, Marina Démoz, Emanuele Albano, and Ciro Isidoro
JCS 2004 117: 1065-1077. [Abstract] [Full Text]  

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 Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content