Nitric oxide-mediated mechanism of neuronal nitric oxide synthase and inducible nitric oxide synthase expression during hypoxia in the cerebral cortex of newborn piglets

Mishra, Om P.; Mishra, R.; Ashraf, Qazi M.; Delivoria‐Papadopoulos, Maria

doi:10.1016/j.neuroscience.2006.02.060

Cited by 27 publications

(23 citation statements)

References 32 publications

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“…In the brain, some of the adaptive hypoxic responses are regulated by nitric oxide (NO) (Mishra et al, 2006), and the molecule has a key role in mitochondrial biogenesis in adipocyte and fibroblast lines via soluble guanylate cyclase-sensitive (sGC) cGMPdependent induction of PGC-1␣ (Nisoli et al, 2003(Nisoli et al, , 2004. The hippocampus is particularly vulnerable to global hypoxia, and we have demonstrated that mitochondrial biogenesis occurs in this brain region in response to the oxidative stress of extreme hyperoxia (Gutsaeva et al, 2006).…”

Section: Introductionmentioning

confidence: 85%

“…Hypoxia activates nNOS and increases its expression, thereby implicating it as an important trigger for the hypoxic responses in the nervous system (Castro-Blanco et al, 2003;Encinas et al, 2004;Mishra et al, 2006). In other tissues, such as brown fat, NO derived from eNOS is required for basal and cold-induced mitochondrial biogenesis (Nisoli et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

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Transient Hypoxia Stimulates Mitochondrial Biogenesis in Brain Subcortex by a Neuronal Nitric Oxide Synthase-Dependent Mechanism

Gutsaeva¹,

Carraway²,

Suliman³

et al. 2008

J. Neurosci.

168

112

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The adaptive mechanisms that protect brain metabolism during and after hypoxia, for instance, during hypoxic preconditioning, are coordinated in part by nitric oxide (NO). We tested the hypothesis that acute transient hypoxia stimulates NO synthase (NOS)-activated mechanisms of mitochondrial biogenesis in the hypoxia-sensitive subcortex of wild-type (Wt) and neuronal NOS (nNOS) and endothelial NOS (eNOS)-deficient mice. Mice were exposed to hypobaric hypoxia for 6 h, and changes in immediate hypoxic transcriptional regulation of mitochondrial biogenesis was assessed in relation to mitochondrial DNA (mtDNA) content and mitochondrial density. There were no differences in cerebral blood flow or hippocampal PO 2 responses to acute hypoxia among these strains of mice. In Wt mice, hypoxia increased mRNA levels for peroxisome proliferator-activated receptor-␥ coactivator-1␣ (PGC-1 ␣), nuclear respiratory factor-1, and mitochondrial transcription factor A. After 24 h, new mitochondria, localized in reporter mice expressing mitochondrial green fluorescence protein, were seen primarily in hippocampal neurons. eNOS Ϫ/Ϫ mice displayed lower basal levels but maintained hypoxic induction of these transcripts. In contrast, nuclear transcriptional regulation of mitochondrial biogenesis in nNOS Ϫ/Ϫ mice was normal at baseline but did not respond to hypoxia. After hypoxia, subcortical mtDNA content increased in Wt and eNOS Ϫ/Ϫ mice but not in nNOS Ϫ/Ϫ mice. Hypoxia stimulated PGC-1␣ protein expression and phosphorylation of protein kinase A and cAMP response element binding (CREB) protein in Wt mice, but CREB only was activated in eNOS Ϫ/Ϫ mice and not in nNOS Ϫ/Ϫ mice. These findings demonstrate that hypoxic preconditioning elicits subcortical mitochondrial biogenesis by a novel mechanism that requires nNOS regulation of PGC-1␣ and CREB.

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Section: Introductionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Transient Hypoxia Stimulates Mitochondrial Biogenesis in Brain Subcortex by a Neuronal Nitric Oxide Synthase-Dependent Mechanism

Gutsaeva¹,

Carraway²,

Suliman³

et al. 2008

J. Neurosci.

168

112

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show abstract

“…It was reported that NO, one of free radicals and cell signaling molecules, could mediate the death of neurons as a toxic factor [7,8] . As a whole, cNOS is thought to have a protective role in injured tissue by increasing the level of cGMP and further modulating the tone of vascular smooth muscles to modify local blood flow, but there are still great differences between the options of nNOS and eNOS [9] . Endothelial NOS can protect disruption of the blood-brain barrier after ischemia [10] .…”

Section: Discussionmentioning

confidence: 99%

Minocycline attenuates cognitive impairment and restrains oxidative stress in the hippocampus of rats with chronic cerebral hypoperfusion

et al. 2008

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Objective Nitric oxide (NO) was speculated to play an important role in the pathophysiology of cerebral ischemia. Minocycline, a tetracycline derivative, reduced inflammation and protected against cerebral ischemia. To study the neuroprotection mechanism of minocycline for vascular dementia, the influences of minocycline on expressions of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) were observed in the brains of Wistar rats. Methods The vascular dementia rat model was established by permanent bilateral common carotid arteries occlusion (BCCAO). Wistar rats were divideded into 3 groups randomly: sham-operation group (S group), vascular dementia model group (M group), and minocycline treatment group (MT group). The behaviour was tested with Morris water maze and open-field task. Expressions of iNOS and eNOS were measured by immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). The optical density value was measured by imaging analysis. Percentage of positive cells with iNOS and eNOS expression was analyzed with optical microscope. Results Minocycline attenuated cognitive impairment. Inducible NOS was significantly down-regulated in MT group, compared with that in M group (P < 0.01), while eNOS was significantly up-regulated, compared with that in M group (P < 0.01). The expressions of iNOS and eNOS in M and MT groups were higher than those in S group (P < 0.01). Conclusion Minocycline can down-regulate the expression of iNOS and up-regulate the expression of eNOS in vascular dementia, which restrains apoptosis and oxidative stress to protect neural function.

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“…(Perlman, 2006) Neonatal hypoxia can also upregulate the expression of nitric oxide (NO) synthases in the cerebral cortex, causing increased production of NO which functions as a free radical and also can trigger several neuronal cell death mechanisms, including NMDA receptor and neuronal nuclear membrane modification and transcription of apoptotic genes. (Mishra et al, 2006) Recent studies indicate that inflammatory mediators also contribute to hypoxic-ischemic brain injury, and although hypoxia-ischemia is recognized as a cause of neonatal brain injury, cytokine mediated maternal-fetal infection (sepsis or fetal inflammatory response syndrome) also plays an important role in the pathogenesis of fetal/neonatal brain damage including early periventricular leukomalacia (PVL). (Mishra et al, 2006;Hitti et al, 2001) There are several neuroprotective interventions and experimental models aiming at ameliorating brain injury.…”

Section: Neonatal Brain Injurymentioning

confidence: 99%

“…(Mishra et al, 2006) Recent studies indicate that inflammatory mediators also contribute to hypoxic-ischemic brain injury, and although hypoxia-ischemia is recognized as a cause of neonatal brain injury, cytokine mediated maternal-fetal infection (sepsis or fetal inflammatory response syndrome) also plays an important role in the pathogenesis of fetal/neonatal brain damage including early periventricular leukomalacia (PVL). (Mishra et al, 2006;Hitti et al, 2001) There are several neuroprotective interventions and experimental models aiming at ameliorating brain injury. However, few of these interventions have been confirmed as sufficiently safe for clinical use.…”

Section: Neonatal Brain Injurymentioning

confidence: 99%

Oxidative Stress and Antioxidants: Preterm Birth and Preterm Infants

Knuppel¹,

Hassan²,

McDermott³

et al. 2012

Preterm Birth - Mother and Child

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Nitric oxide-mediated mechanism of neuronal nitric oxide synthase and inducible nitric oxide synthase expression during hypoxia in the cerebral cortex of newborn piglets

Cited by 27 publications

References 32 publications

Transient Hypoxia Stimulates Mitochondrial Biogenesis in Brain Subcortex by a Neuronal Nitric Oxide Synthase-Dependent Mechanism

Transient Hypoxia Stimulates Mitochondrial Biogenesis in Brain Subcortex by a Neuronal Nitric Oxide Synthase-Dependent Mechanism

Minocycline attenuates cognitive impairment and restrains oxidative stress in the hippocampus of rats with chronic cerebral hypoperfusion

Oxidative Stress and Antioxidants: Preterm Birth and Preterm Infants

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