Mitochondria nitric oxide synthase in inflammation and septic shock Tu jie
Mitochondria nitric oxide synthase in inflammation and septic shock Tu jie
Nitric Oxide a ubiquitous signaling molecule Chemical characters 2NO+02→2NO2 NO2+NO2→N2O4 n=0 NO2+N0→N2O3 ●● [NO]+OH→HNO2→NO2tH [NO2 ][NO+]+H2O -2NO2+2H+ [NO 3 ][NO*]+H2O>NO2+NO3 2H+
Nitric Oxide a ubiquitous signaling molecule ◼ Chemical characters 2NO+O2 → 2NO2 NO2 + NO2 → N2O4 NO2 +NO → N2O3 [NO+ ] + OH- → HNO2 → NO - 2+ H+ [NO - 2 ][NO+ ] + H2O → 2NO - 2+ 2H+ [NO - 3 ][NO+ ] + H2O → NO - 2+ NO - 3 + 2H+
Parkinson's Disease Programmed Cell Death NO Antimicrobial Agent Cardiovascular Disease Impotence (Viagra)
Biosynthesis of Nitric Oxide H2N NH吃 H2N, N-OH NOS NH NH NADPH +NO BH4 02 HEME H"3N COO Ca2+/CaM H'3N COO L-arginine L-citrulline
◼ Biosynthesis of Nitric Oxide H2N NH2 + NH H + 3N COOH2N N-OH NH H + 3N COONADPH + NO BH4 O2 HEME Ca2+/CaM NOS L-arginine L-citrulline
Three isoforms of NOS Glutamate NMDA民 p595 CaM BH Neurotransmission
Three isoforms of NOS
Acetylcholine NO Ach-R eNOS +》2 PKA ●Ca2 eNOS Inactive BHa CaM
IFN-Y Jak-1 Jak-2 STAT-1 STAT.T N⊙5 STAT-1 00
3 Bw/owu) 20406080 Time (sec) Fig.1.Time-dependent NO formation in mitochondrial subfractions measured spectrophotometricaly.NO formation by BM (and SMP (was measured by following the conversion of HbO,to metHb at 401 nm.Inhibition by 1 mM L-NMMA of NO formation is shown for BM (and SMP ()Each point represents the meanS.E.M.of eight independent experiments
Cellular and mitochondrial production of NO ◼ A fourth type of NOS: mitochondrial NOS (mtNOS) 1. first observed in rat liver mitochondria by Ghafourifar group and Giulivi group, 1997-1998; 2. localize in the mitochondrial innermembrane
3.mtNOS activity is substantial and modulated by calcium L-NMMA 4.mtNOS continously controls mitochondrial respiration 20 60 d cat+added〔mol/mg) 33uM02 Respiration of IM is markedly inhibited 1 min when mtNOS is stimulated (trace b vs 6 trace a)
3. mtNOS activity is substantial and modulated by calcium 4. mtNOS continously controls mitochondrial respiration Respiration of IM is markedly inhibited when mtNOS is stimulated （trace b vs trace a)
The role of mtNOS in inflammation and septic shock Trauma Inflammation and septic shock Sepsis A com bination of three clinical signs: Infection SIRS Burns Septic vasodilation,hyperthermia, Shock edema Pancreatitis Myochondrial dysfunction septic shock:a major cause of death
Infection SIRS Sepsis Trauma Burns Pancreatitis ◼ Inflammation and septic shock • A combination of three clinical signs: vasodilation, hyperthermia, edema • Myochondrial dysfunction The role of mtNOS in inflammation and septic shock Septic Shock septic shock: a major cause of death