S-nitrosothiols and nitric oxide, but not sodium nitroprusside, protect nigrostriatal dopamine neurons against iron-induced oxidative stress in vivo

Rauhala, Pekka; Mohanakumar, Kochupurackal P.; Sziráki, István; Lin, Anya Maan Yuh; Chiueh, Chuang C.

doi:10.1002/(sici)1098-2396(199605)23:1<58::aid-syn7>3.0.co;2-g

Cited by 92 publications

(65 citation statements)

References 13 publications

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“…Specifically, neuroprotective and antioxidant effects of RSNO have been described (Rauhala et al, 1996). One potential mechanism of neuroprotection by RSNO involves S-nitrosylation of free thiols at the redox modulatory site of the N-methyl-D-aspartate receptor (Lipton et al, 1993).…”

mentioning

confidence: 99%

Increased S-Nitrosothiols and S-Nitrosoalbumin in Cerebrospinal Fluid after Severe Traumatic Brain Injury in Infants and Children: Indirect Association with Intracranial Pressure

Bayır

Kochanek

Liu

et al. 2003

J Cereb Blood Flow Metab

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Summary: Nitric oxide (NO) is implicated in both secondary damage and recovery after traumatic brain injury (TBI). Transfer of NO groups to cysteine sulfhydryls on proteins produces S-nitrosothiols (RSNO). S-nitrosothiols may be neuroprotective after TBI by nitrosylation of N-methyl-D-aspartate receptor and caspases. S-nitrosothiols release NO on decomposition for which endogenous reductants (i.e., ascorbate) are essential, and ascorbate is depleted in cerebrospinal fluid (CSF) after pediatric TBI. This study examined the presence and decomposition of RSNO in CSF and the association between CSF RSNO level and physiologic parameters after severe TBI. Cerebrospinal fluid samples (n ‫ס‬ 72) were obtained from 18 infants and children on days 1 to 3 after severe TBI (Glasgow Coma Scale score < 8) and 18 controls. Cerebrospinal fluid RSNO levels assessed by fluorometric assay peaked on day 3 versus control (1.42 ± 0.11 mol/L vs. 0.86 ± 0.04, P < 0.05). Snitrosoalbumin levels were also higher after TBI (n ‫ס‬ 8, 0.99 ± 0.09 mol/L on day 3 vs. n ‫ס‬ 6, 0.42 ± 0.02 in controls, P < 0.05). S-nitrosoalbumin decomposition was decreased after TBI. Multivariate analysis showed an inverse relation between CSF RSNO and intracranial pressure and a direct relation with barbiturate treatment. Using a novel assay, the presence of RSNO and S-nitrosoalbumin in human CSF, an ∼1.7-fold increase after TBI, and an association with low intracranial pressure are reported, supporting a possible neuroprotective role for RSNO. The increase in RSNO may result from increased NO production and/or decreased RSNO decomposition. Key Words: Nitric oxide-Nitrosative stress-Oxidative stressHead injury-Ascorbate-DAF-2.Although the primary event in traumatic brain injury (TBI) is direct disruption of brain parenchyma, a significant amount of damage results from a secondary cascade of biochemical, cellular, and molecular events (Kochanek et al., 2000). Secondary insults contribute to evolution of damage, protection, and repair, thus providing a variety of therapeutic targets.Nitric oxide (NO) is implicated in both injury (Dawson et al., 1994) and neurologic recovery (Holscher, 1997) after brain injury. The location, timing, and amount of NO production may determine its role, as well as the type of injury sustained (Iadocola et al., 1995;Lipton et al., 1993). Nitric oxide is synthesized by at least three known isoforms of NO synthase (NOS). Nitric oxide produced by endothelial NOS (eNOS) provides benefit in models of TBI (DeWitt et al., 1997). Nitric oxide produced by neuronal NOS (nNOS) contributes to neuronal damage after ischemic or excitotoxic insults (Huang et al., 1994;Schulz et al., 1995). Nitric oxide derived from inducible NOS (iNOS) may contribute to either secondary damage (Wada et al., 1998a) or recovery (Sinz et al., 1999) plasma, erythrocytes, platelets, and leukocytes, and in rat cerebellum (Stamler et al., 1992;Kluge et al., 1997;Gaston, 1999;Kelm, 1999;Gladwin et al., 2000). Steadystate concentrations of RSNO are tissue specific and depe...

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confidence: 99%

Increased S-Nitrosothiols and S-Nitrosoalbumin in Cerebrospinal Fluid after Severe Traumatic Brain Injury in Infants and Children: Indirect Association with Intracranial Pressure

Bayır

Kochanek

Liu

et al. 2003

J Cereb Blood Flow Metab

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“…, which would lead to formation of a potent cytotoxic peroxynitrite, ONOO Ϫ ) (11,12). Cytoprotective and antioxidant properties of RS-NO were recently confirmed in studies in vitro and in vivo (13)(14)(15)(16).…”

mentioning

confidence: 99%

Nitrosothiol Formation Catalyzed by Ceruloplasmin

Inoue¹,

Akaike²,

Miyamoto³

et al. 1999

Journal of Biological Chemistry

187

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Ceruloplasmin (CP) is a major multicopper-containing plasma protein that is not only involved in iron metabolism through its ferroxidase activity but also functions as an antioxidant. However, physiological substrates for CP have not been fully identified nor has the role of CP been fully understood. The reaction of nitric oxide (NO) with CP was investigated in view of nitrosothiol (RS-NO) formation. First, formation of heavy metal-or CP-catalyzed RS-NO was examined with physiologically relevant concentrations of NO and various thiol compounds (RSH) such as glutathione (GSH). Among the various heavy metal ions and copper-containing enzymes and proteins examined, only copper ion (Cu 2؉ ) and CP showed potent RS-NO (S-nitrosoglutathione)-producing activity. Also, RS-NO-forming catalytic activity was evident for CP added exogenously to RAW264 cells expressing inducible NO synthase in culture, but this was not the case for copper ion. Similarly, CP produced endogenously by HepG2 cells showed potent RS-NO-forming activity in the cell culture. One-electron oxidation of NO appears to be operative for RS-NO production via electron transfer from type 1 copper to a cluster of types 2 and 3 copper in CP. Neurological disorders are associated with aceruloplasminemia; besides RS-NO, S-nitrosoglutathione particularly has been shown to have neuroprotective effect against oxidative stress induced by iron overload. Thus, we suggest that CP plays an important catalytic role in RS-NO formation, which may contribute to its potent antioxidant and cytoprotective activities in vivo in mammalian biological systems.

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“…Under certain conditions (24), low molecular weight S-nitrosothiols have also been shown to be neuroprotective (39,40). Indeed, GSNO appears to be concentrated in the central nervous system on the order of 6 -8 M (41).…”

Section: Amyotrophic Lateral Sclerosis (Als)mentioning

confidence: 99%

“…Higher enzyme concentrations may further exaggerate S-nitrosothiol breakdown by WT SOD and mutant SODs. Over time, this could have a detrimental effect on neuronal survival given the neuroprotective effects of low molecular weight S-nitrosothiols (24,39,40).…”

Section: S-nitrosylation Of Caspases As Well As the N-methyl-d-as-mentioning

confidence: 99%

“…These include immune functions (15), inhibition of oxidant response enzymes (16 -23), modulation of ion channel conductivity (24 -27), and antimicrobial effects (17,29,30). Additionally, S-nitrosothiols have been proposed to have a role in bronchodilation (31-33) and vasodilation (34 -38).Under certain conditions (24), low molecular weight S-nitrosothiols have also been shown to be neuroprotective (39,40). Indeed, GSNO appears to be concentrated in the central nervous system on the order of 6 -8 M (41).…”

mentioning

confidence: 95%

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Accelerated S-Nitrosothiol Breakdown by Amyotrophic Lateral Sclerosis Mutant Copper,Zinc-Superoxide Dismutase

Johnson¹,

Macdonald²,

Mannick³

et al. 2001

Journal of Biological Chemistry

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Mutations in copper,zinc-superoxide dismutase (SOD) have been implicated in familial amyotrophic lateral sclerosis (FALS). We have investigated the breakdown of S-nitrosothiols by wild-type (WT) SOD and two common FALS mutants, alanine-4 valine (A4V) SOD and glycine-37 arginine (G37R) SOD. In the presence of glutathione, A4V SOD and G37R SOD catalyzed S-nitrosoglutathione breakdown three times more efficiently than WT SOD. Indeed, A4V SOD catabolized GSNO more efficiently than WT SOD throughout the physiological range of GSH concentrations. Moreover, a variety of additional S-nitrosothiols were catabolized more readily by A4V SOD than by WT SOD. Initial rate data for fully reduced WT SOD and A4V SOD, and data using ascorbic acid as the reductant, suggest that FALS mutations in SOD may influence the efficiency of reduction of the copper center by glutathione. We have identified a potentially toxic gain of function of two common FALS mutations that may contribute to neurodegeneration in FALS. Amyotrophic lateral sclerosis (ALS)1 is a fatal disorder characterized by the degradation of motor neurons in the cerebral cortex, brain stem, and spinal cord (1). The average age of onset is 55 years with complete paralysis and death resulting two to five years after the appearance of symptoms (2). Although the cause of ALS remains unknown, recent breakthroughs have linked ϳ20% of familial ALS (FALS) cases to any one of more that 90 different autosomal dominant mutations in sod1, the gene encoding copper,zinc-superoxide dismutase (SOD) (3).Since this discovery, considerable effort has gone into determining the underlying mechanisms of motor neuron damage caused by ALS mutant SOD. In 1994, Gurney and co-workers (4) found that mice expressing both FALS mutant SOD and their own SOD developed ALS symptoms, suggesting that FALS mutant SODs cause motor neuron damage by a toxic gain of function. Proposals for this gain of function include aberrant oxidative reactions (5, 6), tyrosine nitration (7-11), and polymerization of mutant SODs (12, 13). Recently, Jourd'heuil and co-workers (14) demonstrated that wild-type bovine CuZn-SOD catalyzes the decomposition of S-nitrosoglutathione (GSNO) and other low molecular weight S-nitrosothiols in the presence of a reductant such as reduced glutathione (GSH). It is therefore possible that a fourth gain of function of mutant SOD involves increased S-nitrosothiol breakdown.S-Nitrosothiols exhibit a wide range of physiological functions. These include immune functions (15), inhibition of oxidant response enzymes (16 -23), modulation of ion channel conductivity (24 -27), and antimicrobial effects (17,29,30). Additionally, S-nitrosothiols have been proposed to have a role in bronchodilation (31-33) and vasodilation (34 -38).Under certain conditions (24), low molecular weight S-nitrosothiols have also been shown to be neuroprotective (39,40). Indeed, GSNO appears to be concentrated in the central nervous system on the order of 6 -8 M (41). One potential mechanism of neuroprotection by S-nitrosothiol...

show abstract

S-nitrosothiols and nitric oxide, but not sodium nitroprusside, protect nigrostriatal dopamine neurons against iron-induced oxidative stress in vivo

Cited by 92 publications

References 13 publications

Increased S-Nitrosothiols and S-Nitrosoalbumin in Cerebrospinal Fluid after Severe Traumatic Brain Injury in Infants and Children: Indirect Association with Intracranial Pressure

Increased S-Nitrosothiols and S-Nitrosoalbumin in Cerebrospinal Fluid after Severe Traumatic Brain Injury in Infants and Children: Indirect Association with Intracranial Pressure

Nitrosothiol Formation Catalyzed by Ceruloplasmin

Accelerated S-Nitrosothiol Breakdown by Amyotrophic Lateral Sclerosis Mutant Copper,Zinc-Superoxide Dismutase

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