"Oxida\u010Dn\u00ED stres zp\u016Fsobovan\u00FD blokov\u00E1n\u00EDm protonov\u00E9 pumpy komplexu I jako chyb\u011Bj\u00EDc\u00ED \u010Dl\u00E1nek neodvratn\u00E9ho cyklu st\u00E1rnut\u00ED a nemoci"@cs . "RIV/67985823:_____/08:00314588!RIV09-MZ0-67985823" . . "Oxidative stress caused by blocking of mitochondrial Complex I Hplus pumping as a link in aging/disease vicious cycle"@en . "Oxidative stress caused by blocking of mitochondrial Complex I Hplus pumping as a link in aging/disease vicious cycle" . . "[68DE74187B9C]" . . . . "Oxidative stress caused by blocking of mitochondrial Complex I Hplus pumping as a link in aging/disease vicious cycle"@en . "RIV/67985823:_____/08:00314588" . "3"^^ . "Hlavat\u00E1, Lydie" . "258052000017" . "Dlaskov\u00E1, Andrea" . "aging/oxidative stres related diseases; mitochondrial superoxide production; mitochondrial Complex I"@en . "1357-2725" . . "3"^^ . . . . . . "International Journal of Biochemistry and Cell Biology" . . "9" . . . . "Oxidative stress caused by blocking of mitochondrial Complex I Hplus pumping as a link in aging/disease vicious cycle" . . "14"^^ . "40" . "GB - Spojen\u00E9 kr\u00E1lovstv\u00ED Velk\u00E9 Brit\u00E1nie a Severn\u00EDho Irska" . "Matrix-released superoxide production, the un-dismuted surplus (Jm) monitored by MitoSOX confocal microscopy was enhanced 5-fold with rotenone. This maximum was attenuated by uncoupling, membrane potential, and pH-collapse. A hydrophobic amiloride that acts on the ND5 subunit and inhibits Complex I Hplus pumping countered the FCCP. Consequently, we have revealed a new principle predicting that Complex I produces maximum superoxide only when both electron transport and Hplus pumping are retarded. We predict that in a vicious cycle, when oxidative stress leads to higher fraction of e.g. mutated ND5 subunits, it will be accelerated more and more. Thus, inhibition of Complex I Hplus pumping, which leads to oxidative stress, appears to be a missing link in the theory of mitochondrial aging and in the etiology of diseases related to oxidative stress" . . "Je\u017Eek, Petr" . . . . "385716" . "P(GA301/05/0221), P(GP303/05/P100), P(IAA500110701), P(NR7917), Z(AV0Z50110509)" . "Superoxid vyl\u00E9van\u00FD do matrix in situ mitochondri\u00ED HEPG2 bun\u011Bk byl konfok\u00E1ln\u011B mikroskopicky monitorov\u00E1n pomoc\u00ED sondy MitoSOX a byl zv\u00FD\u0161en 5kr\u00E1t pom p\u0159id\u00E1n\u00ED rotenonu. Tento maxim\u00E1ln\u00ED v\u00FDlev byl naopak sn\u00ED\u017Een odp\u0159a\u017Een\u00EDm, kolapsem membr\u00E1nov\u00E9ho potenci\u00E1lu \u010Di pH. Hydrofobn\u00ED amilorid inhibuj\u00EDc\u00ED ND5 podjednotku komlexu I a jej\u00ED pumpov\u00E1n\u00ED proton\u016F zamezil efektu odp\u0159a\u017Een\u00ED. Odvodili jsme tak nov\u00FD princip, kdy komplex I produkuje superoxid pouze za sou\u010Dasn\u00E9ho zpomalen\u00ED pumpov\u00E1n\u00ED proton\u016F i p\u0159enosu elektron\u016F. P\u0159i tzv. nevyhnuteln\u00E9m cyklu samozesiluj\u00EDc\u00EDho se oxida\u010Dn\u00EDho stresu u st\u00E1rnut\u00ED a rozvoje n\u011Bkter\u00FDch nemoc\u00ED je tak inhibice pumpov\u00E1n\u00ED proton\u016F na komplexu I spojovac\u00EDm \u010Dl\u00E1nkem umo\u017E\u0144uj\u00EDc\u00ED n\u00E1sledovn\u00FD sled cyklu. Inhibice vede k oxida\u010Dn\u00EDmu stresu, jen\u017E zmutuje p\u0159\u00EDslu\u0161nou podjednotku, t\u00EDm indukuje dal\u0161\u00ED oxida\u010Dn\u00ED stres"@cs . "Oxida\u010Dn\u00ED stres zp\u016Fsobovan\u00FD blokov\u00E1n\u00EDm protonov\u00E9 pumpy komplexu I jako chyb\u011Bj\u00EDc\u00ED \u010Dl\u00E1nek neodvratn\u00E9ho cyklu st\u00E1rnut\u00ED a nemoci"@cs . . . "Matrix-released superoxide production, the un-dismuted surplus (Jm) monitored by MitoSOX confocal microscopy was enhanced 5-fold with rotenone. This maximum was attenuated by uncoupling, membrane potential, and pH-collapse. A hydrophobic amiloride that acts on the ND5 subunit and inhibits Complex I Hplus pumping countered the FCCP. Consequently, we have revealed a new principle predicting that Complex I produces maximum superoxide only when both electron transport and Hplus pumping are retarded. We predict that in a vicious cycle, when oxidative stress leads to higher fraction of e.g. mutated ND5 subunits, it will be accelerated more and more. Thus, inhibition of Complex I Hplus pumping, which leads to oxidative stress, appears to be a missing link in the theory of mitochondrial aging and in the etiology of diseases related to oxidative stress"@en .