Nitrobenzylthioinosine (NBT), a nucleoside transport inhibitor, protects against Shiga toxin cytotoxicity in human microvascular endothelial cells.
Infections with Shiga toxin (Stx)-producing Escherichia coli (STEC) cause microvascular endothelial cell damage, resulting in hemorrhagic colitis and hemolytic uremic syndrome. The prevention of endothelial cell damage is therefore a crucial step in overcoming this disorder. Here, we report that nitrobenzylthioinosine (NBT), a nucleoside transport inhibitor, has a protective effect against the cytotoxicity of Stxs in human microvascular endothelial cells (HMVECs). The relative viability of cells treated with 1.5-15 pM of Stx1 was reduced to 10-20% of that without Stx1. However, the viability of cells treated with NBT (10-100 microM) remained higher than 80%, even in the presence of Stx1. NBT also protected against Stx1 cytotoxicity in sodium butyrate-treated hypersensitive HMVECs. The protective effect of NBT against Stx cytotoxicity may be due to the depletion of ATP in the cells, thereby inhibiting the entry of Stx1.
Ohmi
K
K
Department of Pathology, National Children's Medical Research Center, Tokyo, Japan.
Kiyokawa
N
N
Sekino
T
T
Suzuki
T
T
Mimori
K
K
Taguchi
T
T
Nakajima
H
H
Katagiri
Y U
YU
Fujimoto
J
J
Nakao
H
H
Takeda
T
T
D000255:Adenosine Triphosphate / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D033703:Nucleoside Transport Proteins / Q000037:antagonists & inhibitors; D020011:Protective Agents / Q000494:pharmacology; D022621:Shiga Toxin / Q000633:toxicity*; D013868:Thioinosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014471:Umbilical Veins
D033703:Nucleoside Transport Proteins; D020011:Protective Agents; D013868:Thioinosine; D022621:Shiga Toxin; D000255:Adenosine Triphosphate; C001789:4-nitrobenzylthioinosine