Mitochondrial nitric oxide synthase is constitutively active and is functionally upregulated in hypoxia

Lacza, Zsombor; Puskar, Michelle; Figueroa, Jorge; Zhang, Jie; Rajapakse, Nishadi; Busija, David W.

doi:10.1016/s0891-5849(01)00754-7

Cited by 126 publications

(69 citation statements)

References 32 publications

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“…It is known that NO competes with SOD for the removal of O 2 • − by forming ONOO-, when NO concentration is in range of mitochondrial SOD level [37]. This process is enhanced during hypoxia when mitochondrial nitricoxide synthase is functionally upregulated [38].…”

Section: Discussionmentioning

confidence: 99%

Effects of intermittent hypoxia different regimes on mitochondrial lipid peroxidation and glutathione-redox balance in stressed rats

Gonchar

2008

Open Life Sciences

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Abstract:The purpose of this study was to compare the influence of two regimes of intermittent hypoxia (IH) [repetitive 5 cycles of 5 min hypoxia (7% O 2 or 12% O 2 in N 2 ) followed by 15 min normoxia, daily for three weeks] on oxidative stress protective systems in liver mitochondria. To estimate the effectiveness of hypoxia adaptation at the early and late preconditioning period, we exposed rats to acute 6-h immobilization at the 1 st and 45 th days after cessation of IH. We showed that severity of hypoxic episodes during IH might initiate different adaptive programs. Moderate hypoxia during IH prevents mitochondrial glutathione pool depletion induced by immobilization stress, maintains GSH-redox cycle via activation of glutathione peroxidase, glutathione-S-transferase, glutathione reductase, NADP + -dependent isocitrate dehydrogenase, and increases Mn-SOD activity. Such regimen of hypoxic preconditioning caused the decrease of mitochondrial superoxide anion generation as well as of basal and stimulated in vitro lipid peroxidation and this protective effect remained for 45 days under renormoxic conditions. Hypoxic adaptation in a more severe regimen exerted beneficial effects on the mitochondrial antioxidant defense system only at its later phase.

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Section: Discussionmentioning

confidence: 99%

Effects of intermittent hypoxia different regimes on mitochondrial lipid peroxidation and glutathione-redox balance in stressed rats

Gonchar

2008

Open Life Sciences

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“…Cytosolic and mitochondrial NOS expression have been shown to be strongly regulated during postnatal brain development: whereas cytosolic NOS expression increases during the first 3 months of postnatal life, mitochondrially localized (mtNOS) expression is highest immediately before birth and during the first week of life (Riobo et al, 2002), becoming undetectable in the adult (Lacza et al, 2004). mtNOS has been extensively characterized in liver, heart, and kidney (Ghafourifar and Richter, 1997;Bringold et al, 2000;Lacza et al, 2001;Boveris et al, 2003;Giulivi, 2003). Producing 1-2 nmol NO per minute per milligram of protein in intact mitochondria (Giulivi et al, 1998), mtNOS has been localized to mitochondria using biochemical and porphyrinic microsensor techniques (Kanai et al, 2001) and by immunohistochemical colocalization.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial Nitric Oxide Mediates Decreased Vulnerability of Hippocampal Neurons from Immature Animals to NMDA

Marks¹,

Boriboun²,

Wang³

2005

J. Neurosci.

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“…In addition, a possibly novel isoform of NOS (mtNOS) is constitutively present in mitochondria, is Ca ++ -dependent (Giulivi, 2003) and appears to be involved in mitochondrial respiratory regulation (Elfering et al, 2002). Under hypoxic conditions, mtNOS activity is induced in comparison to that seen in non-stressed mitochondria (Lacza et al, 2001). In rat liver mitochondria, mtNOS has been shown to stimulated by Ca ++ influx (Ghafourifar and Richter, 1997) and leads to intramitochondrial PN formation (Ghafourifar et al, 1999).…”

Section: Sources Of Peroxynitritementioning

confidence: 99%

Temporal relationship of peroxynitrite-induced oxidative damage, calpain-mediated cytoskeletal degradation and neurodegeneration after traumatic brain injury

Deng

Thompson

Gao

et al. 2007

Experimental Neurology

131

168

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We assessed the temporal and spatial characteristics of PN-induced oxidative damage and its relationship to calpain-mediated cytoskeletal degradation and neurodegeneration in a severe unilateral controlled cortical impact (CCI) traumatic brain injury (TBI) model. Quantitative temporal time-course studies were performed to measure two oxidative damage markers: 3-nitrotyrosine (3NT) and 4-hydroxynonenal (4HNE) at 30 min, 1, 3, 6, 12, 24, 48, 72 hrs, 7 days after injury in ipsilateral cortex of young adult male CF-1 mice. Secondly, the time course of Ca ++ -activated, calpain-mediated proteolysis was also analyzed using quantitative western-blot measurement of breakdown products of the cytoskeletal protein α-spectrin. Finally, the time course of neurodegeneration was examined using de Olmos silver staining. Both oxidative damage markers increased in cortical tissue immediately after injury (30 min) and elevated for the first 3-6 hrs before returning to baseline. In the immunostaining study, the PN-selective marker, 3NT, and the lipid peroxidation marker, 4HNE, were intense and overlapping in the injured cortical tissue. α-Spectrin breakdown products, which was used as biomarker for calpain-mediated cytoskeletal degradation, were also increased after injury, but the time course lagged behind the peak of oxidative damage and did not reach its maximum until 24 hrs post-injury. In turn, cytoskeletal degradation preceded the peak of neurodegeneration which occurred at 48 hrs post-injury. These studies have led us to the hypothesis that PN-mediated oxidative damage is an early event that contributes to a compromise of Ca ++ homeostatic mechanisms which causes a massive Ca ++ overload and calpain activation which is a final common pathway that results in post-traumatic neurodegeneration.

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Mitochondrial nitric oxide synthase is constitutively active and is functionally upregulated in hypoxia

Cited by 126 publications

References 32 publications

Effects of intermittent hypoxia different regimes on mitochondrial lipid peroxidation and glutathione-redox balance in stressed rats

Effects of intermittent hypoxia different regimes on mitochondrial lipid peroxidation and glutathione-redox balance in stressed rats

Mitochondrial Nitric Oxide Mediates Decreased Vulnerability of Hippocampal Neurons from Immature Animals to NMDA

Temporal relationship of peroxynitrite-induced oxidative damage, calpain-mediated cytoskeletal degradation and neurodegeneration after traumatic brain injury

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