Send to

Choose Destination
Thromb Res. 2001 May 15;102(4):353-61.

Localized activation of m-calpain in human umbilical vein endothelial cells upon hypoxia.

Author information

Department of Surgery and Clinical Oncology, Graduate School of Medicine, Osaka University, Japan.


Bleb formation is an early event of cellular damage observed in a variety of cell types upon hypoxia. Although we previously found the appearance of the localized cytoplasmic ionized Ca(2+) concentration ([Ca(2+)](i)) rise before bleb formation at the same loci of human umbilical vein endothelial cell (HUVEC) upon hypoxia, the mode of [Ca(2+)](i)-rise-induced cytoskeletal alteration remains ill-defined. The aim of this study is to clarify the mechanisms causing bleb formation after localized [Ca(2+)](i) rise. We studied the activation of m-calpain associated with the alteration of cytoskeleton-related proteins, F-actin, mu-actin, or ezrin by employing specific antibodies in conjunction with a confocal laser scanning microscopy (CLSM). Specific antibodies against 80-kDa-preactivated and 78-kDa-activated m-calpain clearly demonstrated redistribution of 80-kDa m-calpain followed by autoproteolytic activation of m-calpain to the 78-kDa form at the same loci of [Ca(2+)](i) rise in hypoxia-treated HUVECs, which was associated with the decrease of ezrin and the localized appearance of beta-actin at the same loci. In conclusion, hypoxia-induced localized [Ca(2+)](i) rise causes bleb formation at the same loci through m-calpain-catalyzed destruction of cross-linking between plasma membrane and actin filaments.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center