Neuronal NOS-mediated nitration and inactivation of manganese superoxide dismutase in brain after experimental and human brain injury

被引:117
作者
Bayir, Hulya
Kagan, Valerian E.
Clark, Robert S. B.
Janesko-Feldman, Keri
Rafikov, Ruslan
Huang, Zhentai
Zhang, Xiaojing
Vagni, Vincent
Billiar, Timothy R.
Kochanek, Patrick M.
机构
[1] Univ Pittsburgh, Med Ctr, Safar Ctr Resuscitat Res, Pittsburgh, PA 15260 USA
[2] Dept Crit Care Med, Pittsburgh, PA USA
[3] Dept Surg, Pittsburgh, PA USA
[4] Dept Environm & Occupat Hlth & Pharmacol, Pittsburgh, PA USA
关键词
1400W; 7-nitroindazole; controlled cortical impact; head injury; myeloperoxidase;
D O I
10.1111/j.1471-4159.2006.04353.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Manganese superoxide dismutase (MnSOD) provides the first line of defense against superoxide generated in mitochondria. SOD competes with nitric oxide for reaction with superoxide and prevents generation of peroxynitrite, a potent oxidant that can modify proteins to form 3-nitrotyrosine. Thus, sufficient amounts of catalytically competent MnSOD are required to prevent mitochondrial damage. Increased nitrotyrosine immunoreactivity has been reported after traumatic brain injury (TBI); however, the specific protein targets containing modified tyrosine residues and functional consequence of this modification have not been identified. In this study, we show that MnSOD is a target of tyrosine nitration that is associated with a decrease in its enzymatic activity after TBI in mice. Similar findings were obtained in temporal lobe cortical samples obtained from TBI cases versus control patients who died of causes not related to CNS trauma. Increased nitrotyrosine immunoreactivity was detected at 2 h and 24 h versus 72 h after experimental TBI and co-localized with the neuronal marker NeuN. Inhibition and/or genetic deficiency of neuronal nitric oxide synthase (nNOS) but not endothelial nitric oxide synthase (eNOS) attenuated MnSOD nitration after TBI. At 24 h after TBI, there was predominantly polymorphonuclear leukocytes accumulation in mouse brain whereas macrophages were the predominant inflammatory cell type at 72 h after injury. However, a selective inhibitor or genetic deficiency of inducible nitric oxide synthase (iNOS) failed to affect MnSOD nitration. Nitration of MnSOD is a likely consequence of peroxynitrite within the intracellular milieu of neurons after TBI. Nitration and inactivation of MnSOD could lead to self-amplification of oxidative stress in the brain progressively enhancing peroxynitrite production and secondary damage.
引用
收藏
页码:168 / 181
页数:14
相关论文
共 92 条
  • [21] Mitochondrial targets of oxidative stress during renal ischemia/reperfusion
    Cruthirds, DL
    Novak, L
    Akhi, KM
    Sanders, PW
    Thompson, JA
    MacMillan-Crow, LA
    [J]. ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2003, 412 (01) : 27 - 33
  • [22] L-arginine and superoxide dismutase prevent or reverse cerebral hypoperfusion after fluid-percussion traumatic brain injury
    DeWitt, DS
    Smith, TG
    Deyo, DJ
    Miller, KR
    Uchida, T
    Prough, DS
    [J]. JOURNAL OF NEUROTRAUMA, 1997, 14 (04) : 223 - 233
  • [23] Induction of manganese superoxide dismutase in acute spinal cord injury
    Earnhardt, JN
    Streit, WJ
    Anderson, DK
    O'Steen, WA
    Nick, HS
    [J]. JOURNAL OF NEUROTRAUMA, 2002, 19 (09) : 1065 - 1079
  • [24] Management of brain-injured patients by an evidence-based medicine protocol improves outcomes and decreases hospital charges
    Fakhry, SM
    Trask, AL
    Waller, MA
    Watts, DD
    [J]. JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE, 2004, 56 (03): : 492 - 499
  • [25] EXPERIMENTAL SUBARACHNOID HEMORRHAGE - EVENTS RELATED TO ANTIOXIDANT ENZYMATIC SYSTEMS AND EICOSANOID PEROXIDE ENHANCEMENT
    GAETANI, P
    BAENA, RR
    QUAGLINI, S
    BELLAZZI, R
    CAFE, C
    TORRI, C
    MARZATICO, F
    [J]. NEUROCHEMICAL RESEARCH, 1994, 19 (07) : 839 - 844
  • [26] Mitochondrial nitric oxide synthase
    Ghafourifar, P
    Cadenas, E
    [J]. TRENDS IN PHARMACOLOGICAL SCIENCES, 2005, 26 (04) : 190 - 195
  • [27] Biological significance of nitric oxide-mediated protein modifications
    Gow, AJ
    Farkouh, CR
    Munson, DA
    Posencheg, MA
    Ischiropoulos, H
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2004, 287 (02) : L262 - L268
  • [28] KINETICS OF SUPEROXIDE SCAVENGING BY DISMUTASE ENZYMES AND MANGANESE MIMICS DETERMINED BY ELECTRON-SPIN-RESONANCE
    GRAY, B
    CARMICHAEL, AJ
    [J]. BIOCHEMICAL JOURNAL, 1992, 281 : 795 - 802
  • [29] Gray Keith D, 2004, Surg Infect (Larchmt), V5, P166, DOI 10.1089/1096296041839453
  • [30] Quantitative assessment of tyrosine nitration of manganese superoxide dismutase in angiotensin II-infused rat kidney
    Guo, W
    Adachi, T
    Matsui, R
    Xu, SQ
    Jiang, BB
    Zou, MH
    Kirber, M
    Lieberthal, W
    Cohen, RA
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2003, 285 (04): : H1396 - H1403