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001-es BibID:BIBFORM047650
Első szerző:Woodberry, Mitchell
Cím:ATP Depletion Via Mitochondrial F1F0 Complex by Lethal Factor is an Early Event in B. Anthracis-Induced Sudden Cell Death / Mitchell W. Woodberry, Leopoldo Aguilera-Aguirre, Attila Bacsi, Ashok K. Chopra, Alexander Kurosky, Johnny W. Peterson, Istvan Boldogh
Dátum:2009
Megjegyzések:Bacillus anthracis' primary virulence factor is a tripartite anthrax toxin consisting of edema factor (EF), lethal factor (LF)and protective antigen (PA). In complex with PA, EF and LF are internalized via receptor-mediated endocytosis. EF is a calmodulindependentadenylate cyclase that induces tissue edema. LF is a zinc-metalloprotease that cleaves members of mitogen-activated proteinkinase kinases. Lethal toxin (LT: PA plus LF)-induced death of macrophages is primarily attributed to expression of the sensitiveNalp1b allele, inflammasome formation and activation of caspase-1, but early events that initiate these processes are unknown. Herewe provide evidence that an early essential event in pyroptosis of alveolar macrophages is LF-mediated depletion of cellular ATP. Theunderlying mechanism involves interaction of LF with F1F0-complex gamma and beta subunits leading to increased ATPase activity inmitochondria. In support, mitochondrial DNA-depleted MH-S cells have decreased F1F0 ATPase activity due to the lack of F06 and F08polypeptides and show increased resistance to LT. We conclude that ATP depletion is an important early event in LT-induced sudden celldeath and its prevention increases survival of toxin-sensitive cells.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
anthrax lethal factor
mitochondria
F1F0 ATPase
pyroptosis
Megjelenés:Journal of Cell Death. - 2 (2009), p. 25-39. -
További szerzők:Aguilera-Aguirre, Leopoldo Bácsi Attila (1967-) (immunológus) Chopra, Ashok K. Kurosky, Alexander Peterson, Johnny W. Boldogh István
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