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A Novel Caspase Dependent Pathway Is Involved in Apoptosis of Human Endothelial Cells by Shiga Toxins
Author(s) -
Yoshida Tomoaki,
Koide Naoki,
Sugiyama Tsuyoshi,
Mori Isamu,
Yokochi Takashi
Publication year - 2002
Publication title -
microbiology and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.664
H-Index - 70
eISSN - 1348-0421
pISSN - 0385-5600
DOI - 10.1111/j.1348-0421.2002.tb02753.x
Subject(s) - caspase , biology , apoptosis , dna fragmentation , microbiology and biotechnology , brefeldin a , umbilical vein , nlrp1 , cytokine , caspase 8 , caspase 1 , caspase 2 , programmed cell death , immunology , in vitro , biochemistry , endoplasmic reticulum , golgi apparatus
Shiga toxins have been shown to induce apoptosis on primary cultures, but not passaged ones, of human umbilical vein endothelial cells, independent of cytokine pre‐treatment. Here, a peculiar pattern of caspase activation was observed; caspase‐3 and ‐2, but not conventional upstream caspases, were activated at the initial phase of 6 hr, whereas a broad range inhibitor of caspases, VAD‐fmk, but not mono‐specific ones, suppressed DNA fragmentation and cell death. These results suggest additional analogous molecules, which have yet to be delineated, are involved. The requirement of retrograde uptake of toxins was also proved by the intervening effect of brefeldin A.