Peroksinitrit literasi

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    eroxynitrite-induced membrane lipid peroxidation: the cytotoxicpotential of superoxide and nitric oxide.Radi R, Beckman JS, Bush KM, Freeman BA.

    Source

    Department of Anesthesiology, ni!ersity of Ala"ama, Birmingham #$%##.

    A"stract

    &ndothelial cells, macrophages, neutrophils, and neuronal cells generate supero'ide

    ()%*+ and nitric o'ide (.)+ -hich can com"ine to form pero'ynitrite anion ()))*+.

    ero'ynitrite, kno-n to o'idi/e sulfhydryls and to yield products indicati!e of hydro'yl

    radical (.)0+ reaction -ith deo'yri"ose and dimethyl sulfo'ide, is sho-n herein to induce

    mem"rane lipid pero'idation. ero'ynitrite addition to soy"ean phosphatidylcholine

    liposomes resulted in malondialdehyde and con1ugated diene formation, as -ell as

    o'ygen consumption. 2ipid pero'idation -as greater at acidic and neutral p0, -ith no

    significant lipid pero'idation occurring a"o!e p0 3.$. Addition of ferrous (Fe4%+ or ferric

    (Fe4#+ iron did not enhance lipid pero'ide formation o!er that attri"uta"le to pero'ynitrite

    alone. Diethylenetetraminepentacetic acid (D5A+ or iron remo!al from solutions "y ion*

    e'change chromatography decreased con1ugated diene formation "y %$*$67. 8ron did

    not play an essential role in initiating lipid pero'idation, since D5A and iron depletion of

    reaction systems -ere only partially inhi"itory. 8n contrast, desferrio'amine had an e!en

    greater concentration*dependent inhi"itory effect, completely a"olishing lipid

    pero'idation at %66 microM. 5he strong inhi"itory effect of desferrio'amine on lipid

    pero'idation -as due to direct reaction -ith pero'ynitrous acid in addition to iron

    chelation. 9e conclude that the con1ugate acid of pero'ynitrite, pero'ynitrous acid()))0+, and:or its decomposition products, i.e., .)0 and nitrogen dio'ide (.)%+,

    initiate lipid pero'idation -ithout the re;uirement of iron. 5hese o"ser!ations

    demonstrate a potential mechanism contri"uting to )%*(*+and .)*mediated cytoto'icity.

    eroxynitrite-mediated protein nitration and lipidperoxidation in a mouse model of traumatic brain injury .0all &D, Detloff MR, Johnson K, Kupina

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    5he role of reacti!e o'ygen*induced o'idati!e damage to lipids (i.e., lipid pero'idation,

    2+ and proteins has "een strongly supported in pre!ious -ork. Most nota"ly, a num"er

    of free radical sca!engers and lipid antio'idants ha!e "een demonstrated to "e

    neuroprotecti!e in traumatic "rain in1ury (5B8+ models. 0o-e!er, the specific sources of

    reacti!e o'ygen species (R)S+, the time course of o'idati!e damage and its relationship

    to post*traumatic neurodegeneration in the in1ured "rain ha!e "een incompletely defined.5he present study -as directed at an in!estigation of the role of the R)S, pero'ynitrite

    ()+, in the acute pathophysiology of 5B8 and its temporal relationship to

    neurodegeneration in the conte't of the mouse model of diffuse head in1ury model. Male

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    administration on diaphragmatic force*generating capacity in @+ intact diaphragm muscle

    fi"er "undles (to model the effects produced "y e'posure of muscles to e'tracellular

    pero'ynitrite+ and %+ single skinned diaphragm muscle fi"ers (to model the effects of

    intracellular pero'ynitrite on contractile protein function+ "y e'amining the effects of "oth

    pero'ynitrite and a pero'ynitrite*generating solution, #*morpholinosydnonimine, on force

    !s. p

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    0ydrogen pero'ide is generated in numerous "iological processes and is implicated as

    the main transmitter of redo' signals. Although a strong o'idant, high acti!ation energy

    "arriers make it unreacti!e -ith most "iological molecules. 8t reacts directly -ith thiols,

    "ut for lo-*molecular*-eight thiols and cysteine residues in most proteins, the reaction is

    slo-. 5he most fa!ored reactions of hydrogen pero'ide are -ith transition metal centers,

    selenoproteins, and selected thiol proteins. 5hese include proteins such as catalase,glutathione pero'idases, and pero'iredo'ins, -hich, as -ell as pro!iding antio'idant

    defense, are increasingly "eing considered as targets for signal transmission. 5his

    o!er!ie- descri"es the main "iological reactions of hydrogen pero'ide and takes a

    kinetic approach to identifying likely targets in the cell. 8t also considers diffusion of

    hydrogen pero'ide and constraints to its acting at locali/ed sites.

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