RRC ID 51882
著者 Seike S, Takehara M, Kobayashi K, Nagahama M.
タイトル Role of pannexin 1 in Clostridium perfringens beta-toxin-caused cell death.
ジャーナル Biochim Biophys Acta
Abstract BACKGROUND:Beta-toxin produced by Clostridium perfringens is a key virulence factor of fatal hemorrhagic enterocolitis and enterotoxemia. This toxin belongs to a family of β-pore-forming toxins (PFTs). We reported recently that the ATP-gated P2X7 receptor interacts with beta-toxin. The ATP-release channel pannexin 1 (Panx1) is an important contributor to P2X7 receptor signaling. Hence, we investigated the involvement of Panx1 in beta-toxin-caused cell death.
METHODS:We examined the effect of Panx1 in beta-toxin-induced cell death utilizing selective antagonists, knockdown of Panx1, and binding using dot-blot analysis. Localization of Panx1 and the P2X7 receptor after toxin treatment was determined by immunofluorescence staining.
RESULTS:Selective Panx1 antagonists (carbenoxolone [CBX], probenecid, and Panx1 inhibitory peptide) prevented beta-toxin-caused cell death in THP-1 cells. CBX did not block the binding of the toxin to cells. Small interfering knockdown of Panx1 blocked beta-toxin-mediated cell death through inhibiting the oligomer formation of the toxin. Beta-toxin triggered a transient ATP release from THP-1 cells, but this early ATP release was blocked by CBX. ATP scavengers (apyrase and hexokinase) inhibited beta-toxin-induced cytotoxicity. Furthermore, co-administration of ATP with beta-toxin enhanced the binding and cytotoxicity of the toxin.
CONCLUSIONS:Based on our results, Panx1 activation is achieved through the interaction of beta-toxin with the P2X7 receptor. Then, ATP released by the Panx1 channel opening promotes oligomer formation of the toxin, leading to cell death.
GENERAL SIGNIFICANCE:Pannexin 1 is a novel candidate therapeutic target for beta-toxin-mediated disease.
巻・号 1858(12)
ページ 3150-3156
公開日 2016-12-1
DOI 10.1016/j.bbamem.2016.10.003
PII S0005-2736(16)30330-3
PMID 27720686
MeSH Adenosine Triphosphate / metabolism Apyrase / pharmacology Bacterial Toxins / toxicity* Carbenoxolone / pharmacology Cell Death / drug effects Cells, Cultured Connexins / physiology* Hexokinase / pharmacology Humans Nerve Tissue Proteins / physiology* Receptors, Purinergic P2X7 / physiology
IF 3.411
引用数 7
リソース情報
ヒト・動物細胞 THP-1(RCB1189)