Hypoxia-induced modification of poly (ADP-ribose) polymerase and dna polymerase β activity in cerebral cortical nuclei of newborn piglets: role of nitric oxide

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

doi:10.1016/s0306-4522(03)00166-0

Cited by 35 publications

(28 citation statements)

References 60 publications

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“…In addition, Cohen-Armon et al demonstrated that ERK2 phosphorylation can be modulated by PolyADP-ribose polymerase-1 (PARP-1) which catalyze a posttranslational modification of nuclear proteins by polyADP-ribosylation [27]. PARP-1 activation could play a role in our model as it has been found to be induced by hypoxia in newborn piglets [28]. The importance of the activation of the PI3K/Akt signaling pathway has been demonstrated in an adult rat stroke model, where cerebral infarct was elicited with permanent middle cerebral artery occlusion (pMCAO).…”

Section: Discussionmentioning

confidence: 74%

Active forms of Akt and ERK are dominant in the cerebral cortex of newborn pigs that are unaffected by asphyxia

et al. 2018

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Section: Discussionmentioning

confidence: 74%

Active forms of Akt and ERK are dominant in the cerebral cortex of newborn pigs that are unaffected by asphyxia

et al. 2018

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“…While PARP1 activation can trigger cell death by several different pathways, depletion of NAD(H) and subsequent energy failure is one mechanism that has been demonstrated for neurons in response to hypoglycemia and hypoxia [22][23][24]. In addition, PARP1-mediated cortical neuronal death in response to neonatal hypoxia appears to be nitric oxide-dependent [25]. It is also possible that nitric oxide and other reactive nitrogen species activate the mitochondrial permeability transition [26], thereby lowering fluorescence through loss of mitochondrial matrix pyridine nucleotides.…”

Section: Discussionmentioning

confidence: 99%

Anoxia-Induced Changes in Pyridine Nucleotide Redox State in Cortical Neurons and Astrocytes

Kahraman

Fiskum

2006

Neurochem Res

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NAD(P)H autofluorescence was used to verify establishment of metabolic anoxia using primary cultures of cortical neurons and astrocytes. Cells on cover slips were placed in a chamber and O 2 was displaced by continuous infusion of argon. Perfusionwith medium at PO 2 < 0.4 mm Hg caused an increase in NAD(P)H fluorescence, albeit to levels lower than that obtained with cyanide. Addition of the nitric oxide-generating agent DETA-NO to the hypoxic medium further increased fluorescence to the level with cyanide. Fluorescence under anoxia remained high in the presence of glucose, but declined in neurons and not in astrocytes when glucose was substituted with 2-deoxyglucose. Reoxygenation of neurons resulted in a decline in fluorescence and a loss in fluorescent gradient between fully reduced and fully oxidized (plus respiratory uncoupler). We conclude that (1) DETA-NO is useful for generating metabolic anoxia in the presence of argon (2) Exogenous glucose is necessary to maintain NAD(P)H in a reduced state during metabolic anoxia in neurons but not astrocytes (3) Neurons undergo a partially irreversible decline in NAD(P)H fluorescence during metabolic anoxia and reoxygenation that could contribute to prolonged metabolic failure.

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“…We have demonstrated that administration of a selective inhibitor of neuronal nitric oxide synthase (nNOS), 7-Nitro-indazole, prevented the hypoxia-induced increased activation of caspase-9 in the cerebral cortex of newborn piglets [22]. Furthermore we have demonstrated that nNOS inhibitor prevent the hypoxia-induced increased activation caspase-3 and poly-ADP-ribose polymerase (PARP) and increased nuclear DNA fragmentation [20,22,30]. These studies demonstrate the pivotal role of nitric oxide in caspase-9 activation and subsequent cascade of hypoxic neuronal death.…”

mentioning

confidence: 95%

ATP and cytochrome c-dependent activation of caspase-9 during hypoxia in the cerebral cortex of newborn piglets

Delivoria‐Papadopoulos

Gorn

Ashraf

et al. 2007

Neuroscience Letters

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In previous studies, we have shown that cerebral hypoxia results in increased activity of caspase-9, the initiator caspase, and caspase-3, in the cytosolic fraction of the cerebral cortex of newborn piglets. The present study examines the mechanism of caspase-9 activation during hypoxia and tests the hypothesis that the ATP and cytochrome c-dependent activation of caspase-9 increases in the cytosol of the cerebral cortex of newborn piglets. Newborn piglets were divided into normoxic (Nx, n=4), and hypoxic (Hx, n=4) groups. Anesthetized, ventilated animals were exposed to an FiO 2 of 0.21 (Nx) or 0.07 (Hx) for 60 min. Cerebral tissue hypoxia was documented biochemically by determining levels of ATP and phosphocreatine (PCr). Cytosolic fraction was isolated and passed through a G25-Sephadex column to remove endogenous ATP and cytochrome c. Fractions were collected and protein determined by UV spectrophotometry at 280 nm. Eluted high molecular weight samples from normoxic and hypoxic animals were divided into four subgroups: Subgroup 1 (control), incubated without added ATP and cytochrome c; Subgroup 2, incubated with added ATP; Subgroup 3, incubated with added cytochrome c; and Subgroup 4, incubated with added ATP and cytochrome c. The incubation was carried out at 37° C for 30 min. Following incubation, the protein was separated by 12% SDS PAGE and active caspase-9 was detected using specific active caspase-9 antibody. Protein bands were detected by enhanced chemilumenescence. Protein density was determined by imaging densitometry and expressed as absorbance (OD × mm 2 ). ATP (μmoles/g brain) level was 4.7±0.18 in normoxic, as compared to 1.53±0.16 in hypoxic (p<0.05 vs Nx). PCr (μmoles/g brain) level was 4.03±0.11 in the normoxic and 1.1±0.3 in the hypoxic brain (p<0.05 vs Nx). In the normoxic preparations, active caspase-9 density increased by 9%, 4% and 20% in the presence of ATP, cytochrome c and ATP + cytochrome c, respectively. In the hypoxic preparations, active caspase-9 density increased by 30%, 45% and 60% in the presence of ATP, cytochrome c, and ATP + cytochrome c, respectively. These results show that incubation with ATP, cytochrome c and ATP +cytochrome c result in a significantly increased activation of caspase-9 in the hypoxic group (p<0.05). We conclude that the ATP and cytochrome c dependent activation of caspase-9 is increased during hypoxia. We propose that the ATP and cytochrome c sites of apoptotic protease activating factor I that mediate caspase-9 activation are modified during hypoxia.

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Hypoxia-induced modification of poly (ADP-ribose) polymerase and dna polymerase β activity in cerebral cortical nuclei of newborn piglets: role of nitric oxide

Cited by 35 publications

References 60 publications

Active forms of Akt and ERK are dominant in the cerebral cortex of newborn pigs that are unaffected by asphyxia

Active forms of Akt and ERK are dominant in the cerebral cortex of newborn pigs that are unaffected by asphyxia

Anoxia-Induced Changes in Pyridine Nucleotide Redox State in Cortical Neurons and Astrocytes

ATP and cytochrome c-dependent activation of caspase-9 during hypoxia in the cerebral cortex of newborn piglets

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