Abstract
We have recently reported that global perinatal asphyxia (PA) induces a regionally sustained increase in oxidized glutathione (GSSG) levels and GSSG/GSH ratio, a decrease in tissue-reducing capacity, a decrease in catalase activity, and an increase in apoptotic caspase-3-dependent cell death in rat neonatal brain up to 14 postnatal days, indicating a long-term impairment in redox homeostasis. In the present study, we evaluated whether the increase in GSSG/GSH ratio observed in hippocampus involves changes in glutathione reductase (GR) and glutathione peroxidase (GPx) activity, the enzymes reducing glutathione disulfide (GSSG) and hydroperoxides, respectively, as well as catalase, the enzyme protecting against peroxidation. The study also evaluated whether there is a shift in the metabolism towards the penthose phosphate pathway (PPP), by measuring TIGAR, the TP53-inducible glycolysis and apoptosis regulator, associated with delayed cell death, further monitoring calpain activity, involved in bax-dependent cell death, and XRCC1, a scaffolding protein interacting with genome sentinel proteins. Global PA was induced by immersing fetus-containing uterine horns removed by a cesarean section from on term rat dams into a water bath at 37 °C for 21 min. Asphyxia-exposed and sibling cesarean-delivered fetuses were manually resuscitated and nurtured by surrogate dams. Animals were euthanized at postnatal (P) days 1 or 14, dissecting samples from hippocampus to be assayed for glutathione, GR, GPx (all by spectrophotometry), catalase (Western blots and ELISA), TIGAR (Western blots), calpain (fluorescence), and XRCC1 (Western blots). One hour after delivery, asphyxia-exposed and control neonates were injected with either 100 μl saline or 0.8 mmol/kg nicotinamide, i.p., shown to protect from the short- and long-term consequences of PA. It was found that global PA produced (i) a sustained increase of GSSG levels and GSSG/GSH ratio at P1 and P14; (ii) a decrease of GR, GPx, and catalase activity at P1 and P14; (iii) a decrease at P1, followed by an increase at P14 of TIGAR levels; (iv) an increase of calpain activity at P14; and (v) an increase of XRCC1 levels, but only at P1. (vi) Nicotinamide prevented the effect of PA on GSSG levels and GSSG/GSH ratio, and on GR, GPx, and catalase activity, also on increased TIGAR levels and calpain activity observed at P14. The present study demonstrates that the long-term impaired redox homeostasis observed in the hippocampus of rats subjected to global PA implies changes in GR, GPx, and catalase, and a shift towards PPP, as indicated by an increase of TIGAR levels at P14.
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Abbreviations
- Ac-LLY-AFC:
-
Ac-Leu-Leu-Tyr-7-amino-4-trifluoromethylcoumarin
- AFC:
-
7-amino-4-trifluoromethylcoumarin
- AIF:
-
Apoptosis inducing factor
- AS:
-
Asphyxia-exposed rats
- a.u.:
-
Arbitrary units
- Bax:
-
Bcl-2 associated X protein apoptosis regulator
- Bid:
-
BH3 interacting domain death agonist
- BCA:
-
Bicinchoninic acid
- BSA:
-
Bovine serum albumin
- C:
-
Cerebellum
- CS:
-
Control saline rats
- DTNB:
-
5, 5′-Dithio-bis-[2-nitrobenzoic acid]
- DTT:
-
Dithiothreitol
- ΔA:
-
Changes in absorbance per minute
- EDTA:
-
Ethylenediaminetetraacetic acid
- EGTA:
-
Ethylene glycol-bis (β-aminoethylether)-N, N, N′, N′-tetraacetic acid
- ELISA:
-
Enzyme-linked immunosorbent assay
- GPx:
-
Glutathione peroxidase
- GR:
-
Glutathione reductase
- GSH:
-
Reduced glutathione
- GSSG:
-
Oxidized glutathione
- G22:
-
Gestation day 22
- HI:
-
Hypoxic-ischemic
- HIE:
-
Hypoxic-ischemia encephalopathy
- HRP:
-
Horseradish peroxidase
- H2O2 :
-
Hydrogen peroxide
- H2Od:
-
Distillated water
- HK2:
-
Hexokinase 2
- i.p:
-
Intraperitoneal injection
- IgG (H + L):
-
Immunoglobulin type G (Heavy + Light chains)
- mU/mL:
-
Milliunits enzymatic per milliliter
- NaCl:
-
Sodium chloride
- NAD+ :
-
Oxidized nicotinamide adenine dinucleotide
- NADH:
-
Reduced nicotinamide adenine dinucleotide
- NADP+ :
-
Oxidized β-Nicotinamide adenine dinucleotide 2′-phosphate
- NADPH:
-
Reduced β-Nicotinamide adenine dinucleotide 2′-phosphate
- NADK:
-
NAD+ kinase
- NaF:
-
Sodium fluoride
- NAMPT:
-
Nicotinamide phosphoribosyltransferase
- Nico:
-
Nicotinamide
- NMNAT:
-
Nicotinamide mononucleotide adenyltransferase
- NMN:
-
Nicotinamide mononucleotide
- PA:
-
Perinatal asphyxia
- PARP1:
-
Poly(ADP-ribose) polymerase 1
- PBS:
-
Phosphate buffer saline
- PK:
-
Pyruvate kinase
- PMSF:
-
Phenylmethylsulfonyl fluoride
- PFK1:
-
Phosphofructokinase 1
- PPP:
-
Pentose phosphate pathway
- P:
-
Postnatal day
- TP53:
-
Tumor protein p53
- p53:
-
Cellular tumor antigen p53
- RE:
-
Reticulum endoplasmic
- RIPA:
-
Radio-immune precipitation assay buffer
- ROS:
-
Reactive oxygen species
- R5P:
-
Ribulose-5-phosphate
- SEM:
-
Standard error of the means
- SOD:
-
Superoxide dismutase
- SDS:
-
Sodium dodecyl sulfate
- SDS-PAGE:
-
Sodium dodecyl sulfate polyacrylamide gel
- SSBR:
-
Single-strand break DNA
- TIGAR:
-
TP53-induced glycolysis and apoptosis regulator
- Tris-HCl:
-
Tris(hydroxymethyl)aminoethane-chloride acid buffer
- TBST:
-
Tris-buffered saline containing 0.1% Tween-20
- TNF-alpha:
-
Tumor necrosis factor alpha
- U/ml:
-
Units enzymatic per milliliter
- Veh:
-
Vehicle
- WB:
-
Western blots
- XIAP:
-
X-linked inhibitor of apoptosis protein
- XRCC1:
-
X-ray repair cross-complementing protein 1
References
Ahearne CE, Boylan GB, Murray DM (2016) Short and long term prognosis in perinatal asphyxia: an update. World J Clin Pediatr 5(1):67–74. https://doi.org/10.5409/wjcp.v5.i1.67
Allende-Castro C, Espina-Marchant P, Bustamante D, Rojas-Mancilla E, Neira T, Gutierrez-Hernandez MA, Esmar D, Valdes JL, Morales P, Gebicke-Haerter PJ, Herrera-Marschitz M (2012) Further studies on the hypothesis of PARP-1 inhibition as strategy for lessening the long-term effects produced by perinatal asphyxia: effects of nicotinamide and theophylline on PARP-1 activity in brain and peripheral tissue. Neurotox Res 22:79–90. https://doi.org/10.1007/s12640-012-9310-2
Balteau M, Tajeddine N, de Meester C, Ginion A, Des Rosiers C, Brady NR, Sommereyns C, Horman S, Vanoverschelde JL, Gailly P, Hue L, Bertrand L, Beauloye C (2011) NADPH oxidase activation by hyperglycaemia in cardiomyocytes is independent of glucose metabolism but requires SGLT1. Cardiovasc Res 92(2):237–246. https://doi.org/10.1093/cvr/cvr230
Baud O, Greene AE, Li J, Wang H, Volpe JJ, Rosenberg PA (2004) Glutathione peroxidase-catalase cooperativity is required for resistance to hydrogen peroxide by mature rat oligodendrocytes. J Neurosci 24(7):1531–1540. https://doi.org/10.1523/JNEUROSCI.3989-03.2004
Bensaad K, Tsuruta A, Selak MA, Vidal MN, Nakano K, Bartrons R, Gottlieb E, Vousden KH (2006) TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell. 126(1):107–120. https://doi.org/10.1016/j.cell.2006.05.036
Bentle MS, Reinicke KE, Bey EA, Spitz DR, Bootman DA (2006) Calcium dependent modulation of poly(ADP-ribose) polymerase 1 alters cellular metabolism and DNA repair. J Biol Chem 281(44):33684–33696. https://doi.org/10.1074/jbc.M603678200
Blomgren K, Hagberg H (2005) Free radicals, mitochondria, and hypoxia-ischemia in the developing brain. Brain Pathol 15(3):234–240. https://doi.org/10.1111/j.1750-3639.2005.tb00526.x
Blomgren K, Hallin U, Andersson AL, Puka-Sundvall M, Bahr BA, McRae A, Saido TC, Kawashima S, Hagberg H (1999) Calpastatin is up-regulated in response to hypoxia and is a suicide substrate to calpain after neonatal cerebral hypoxia-ischemia. J Biol Chem 274(20):14046–14052. https://doi.org/10.1074/jbc.274.20.14046
Blomgren K, Zhu C, Wang X, Karlsson JO, Leverin AL, Bahr BA, Mallard C, Hagberg H (2001) Synergistic activation of caspase-3 by m-calpain after neonatal hypoxia-ischemia: a mechanism of “pathological apoptosis”? J Biol Chem 276(13):10191–10198. https://doi.org/10.1074/jbc.M007807200
Bordone L, Campbell C (2002) DNA ligase III is degraded by calpain during cell death induced by DNA-damaging agents. J Biol Chem 277(29):26673–26680. https://doi.org/10.1074/jbc.M112037200
Brekke EM, Morken TS, Widerøe M, Håberg AK, Brubakk AM, Sonnewald U (2014) The pentose phosphate pathway and pyruvate carboxylation after neonatal hypoxic-ischemic brain injury. J Cereb Blood Flow Metab 34(4):724–734. https://doi.org/10.1038/jcbfm.2014.8
Cao L, Chen J, Li M, Qin YY, Sun M, Sheng R, Han F, Wang G, Qin ZH (2015) Endogenous level of TIGAR in brain is associated with vulnerability of neurons to ischemic injury. Neurosci Bull 31(5):527–540. https://doi.org/10.1007/s12264-015-1538-4
Cao L, Zhang D, Chen J, Qin YY, Sheng R, Feng X, Chen Z, Ding Y, Li M, , Qin ZH (2017) G6PD plays a neuroprotective role in brain ischemia through promoting pentose phosphate pathway. Free Radic Biol Med 112: 433–444. https://doi.org/10.1016/j.freeradbiomed.2017.08.011
Chakrabarti G, Gerber DE, Boothman DA (2015) Expanding antitumor therapeutic windows by targeting cancer-specific nicotinamide adenine dinucleotide phosphate-biogenesis pathways. Clin Pharm 7:57–68. https://doi.org/10.2147/CPAA.S79760
Cheng SY, Wang SC, Lei M, Wang Z, Xiong K (2018) Regulatory role of calpaìn in neuronal death. Neural Regen Res 13(3):556–562. https://doi.org/10.4103/1673-5374.228762
Cheung EC, Ludwig RL, Vousden KH (2012) Mitochondrial localization of TIGAR under hypoxia stimulates HK2 and lowers ROS and cell death. Proc Natl Acad Sci U S A 109(50):20491–20496. https://doi.org/10.1073/pnas.1206530109
Chiappe-Gutierrez M, Kitzmueller E, Labudova O, Fuerst G, Hoeger H, Hardmeier R, Nohl H, Gille L, Lubec B (1998) mRNA levels of the hypoxia inducible factor (HIF-1) and DNA repair genes in perinatal asphyxia of the rat. Life Sci 63(13):1157–1167. https://doi.org/10.1016/S0024-3205(98)00377-4
Chong ZZ, Lin SH, Maiese K (2004) The NAD+ precursor nicotinamide governs neuronal survival during oxidative stress through protein kinase B coupled to FOXO3a and mitochondrial membrane potential. J Cereb Blood Flow Metab 24(7):728–743. https://doi.org/10.1097/01.WCB.0000122746.72175.0E
Chua BT, Guo K, Li P (2000) Direct cleavage by the calcium-activated protease calpain can lead to inactivation of caspases. J Biol Chem 275(7):5131–5135. https://doi.org/10.1074/jbc.275.7.5131
da-Silva WS, Gómez-Puyou A, de Gómez-Puyou MT, Moreno-Sanchez R, De Felice FG, de Meis L, Oliveira MF, Galina A (2004) Mitochondrial bound hexokinase activity as a preventive antioxidant defense: steady-state ADP formation as a regulatory mechanism of membrane potential and reactive oxygen species generation in mitochondria. J Biol Chem 279(38):39846–39855. https://doi.org/10.1074/jbc.M403835200
Degasperi A, Birtwistle MR, Volinsky N, Rauch J, Kolch W, Kholodenko BN (2014) Evaluating strategies to normalise biological replicates of Western blot data. PLoS One 9(1):e87293
Dell'Anna E, Chen Y, Engidawork E, Andersson K, Lubec G, Luthman J, Herrera-Marschitz M (1997) Delayed neuronal death following perinatal asphyxia in rat. Exp Brain Res 115:105–115. https://doi.org/10.1007/PL00005670
Deponte M (2013) Glutathione catalysis and the reaction mechanisms of glutathione-dependent enzymes. Biochim Biophys Acta 1830(5):3217–3266. https://doi.org/10.1016/j.bbagen.2012.09.018
D'Orsi B, Bonner H, Tuffy LP, Düssmann H, Woods I, Courtney MJ, Ward MW, Prehn JH (2012) Calpains are downstream effectors of bax-dependent excitotoxic apoptosis. J Neurosci 32(5):1847–1858. https://doi.org/10.1523/JNEUROSCI.2345-11.2012
Dringen R (2000) Metabolism and functions of glutathione in brain. ProgNeurobiol. 62(6):649–671. https://doi.org/10.1016/S0301-0082(99)00060-X
Dringen R, Hamprecht B (1997) Involvement of glutathione peroxidase and catalase in the disposal of exogenous hydrogen peroxide by cultured astroglial cells. Brain Res 759(1):67–75. https://doi.org/10.1016/S0006-8993(97)00233-3
Dunning S, Ur Rehman A, Tiebosch MH, Hannivoort RA, Haijer FW, Woudenberg J, van den Heuvel FA, Buist-Homan M, Faber KN, Moshage H (2013) Glutathione and antioxidant enzymes serve complementary roles in protecting activated hepatic stellate cells against hydrogen peroxide-induced cell death. Biochim Biophys Acta 1832:2027–2034. https://doi.org/10.1016/j.bbadis.2013.07.008
El-Khamisy SF, Masutani M, Suzuki H, Caldecott KW (2003) A requirement for PARP-1 for the assembly or stability of XRCC1 nuclear foci at sites of oxidative DNA damage. Nucleic Acids Res 31(19):5526–5533. https://doi.org/10.1093/nar/gkg761
Ermak G, Davies KJ (2002) Calcium and oxidative stress: from cell signaling to cell death. Mol Immunol 38:713–721. https://doi.org/10.1016/S0161-5890(01)00108-0
Fico A, Paglialunga F, Cigliano L, Abrescia P, Verde P, Martini G, Iaccarino I, Filosa S (2004) Glucose-6-phosphate dehydrogenase plays a crucial role in protection from redox-stress-induced apoptosis. Cell Death Differ 11(8):823–831. https://doi.org/10.1038/sj.cdd.4401420
Fleiss B, Gressens P (2012) Tertiary mechanisms of brain damage: a new hope for treatment of cerebral palsy? Lancet Neurol 11(6):556–566. https://doi.org/10.1016/S1474-4422(12)70058-3
Franco-Enzástiga U, Santana-Martínez RA, Silva-Islas CA, Barrera-Oviedo D, Chánez-Cárdenas ME, Maldonado PD (2017) Chronic administration of S-allylcysteine activates Nrf2 factor and enhances the activity of antioxidant enzymes in the striatum, frontal cortex and hippocampus. Neurochem Res 42:3041–3051. https://doi.org/10.1007/s11064-017-2337-2
Fujimura M, Morita-Fujimura Y, Sugawara T, Chan PH (1999) Early decrease of XRCC1, a DNA base excision repair protein, may contribute to DNA fragmentation after transient focal cerebral ischemia in mice. Stroke 30(11):2456–2463. https://doi.org/10.1161/01.STR.30.11.2456
Ghosh S, Janocha AJ, Aronica MA, Swaidani S, Comhair SA, Xu W, Zheng L, Kaveti S, Kinter M, Hazen SL, Erzurum SC (2006) Nitrotyrosine proteome survey in asthma identifies oxidative mechanism of catalase inactivation. J Immunol 176(9):5587–5597. https://doi.org/10.4049/jimmunol.176.9.5587
Ghosh S, Canugovi C, Yoon JS, Wilson DM 3rd, Croteau DL, Mattson MP, Bohr VA (2015) Partial loss of the DNA repair scaffolding protein, Xrcc1, results in increased brain damage and reduced recovery from ischemic stroke in mice. Neurobiol Aging 36(7):2319–2320. https://doi.org/10.1016/jneurobiolaging.2015.04.004
Gupte SA, Levine RJ, Gupte RS, Young ME, Lionetti V, Labinskyy V, Floyd BC, Ojaimi C, Bellomo M, Wolin MS, Recchia FA (2006) Glucose-6-phosphate dehydrogenase-derived NADPH fuels superoxide production in the failing heart. J Mol Cell Cardiol 41(2):340–349. https://doi.org/10.1016/j.yjmcc.2006.05.003
Hagberg H, David Edwards A, Groenendaal F (2016) Perinatal brain damage: the term infant. Neurobiol Dis 92(Pt A):102–112. https://doi.org/10.1016/j.nbd.2015.09.011
Hassell KJ, Ezzati M, Alonso-Alconada D, Hausenloy DJ (2015) New horizons for newborn brain prtection: enhancing endogenous neuroprotection. Arch Dis Child Fetal Neonatal 100:541–552. https://doi.org/10.1136/archdischild-2014-306284
Herrera-Marschitz M, Morales P, Leyton L, Bustamante D, Klawitter V, Espina-Marchant P, Allende C, Lisboa F, Cunich G, Jara-Cavieres A, Neira T, Gutierrez-Hernandez MA, Gonzalez-Lira V, Simola N, Schmitt A, Morelli M, Andrew Tasker R, Gebicke-Haerter PJ (2011) Perinatal asphyxia: current status and approaches towards neuroprotective strategies, with focus on sentinel proteins. Neurotox Res 19(4):603–627. https://doi.org/10.1007/s12640-010-9208-9
Herrera-Marschitz M, Neira-Pena T, Rojas-Mancilla E, Espina-Marchant P, Esmar D, Perez R, Muñoz V, Gutierrez-Hernandez M, Rivera B, Simola N, Bustamante D, Morales P, Gebicke-Haerter PJ (2014) Perinatal asphyxia: CNS development and deficits with delayed onset. Front Neurosci 8(47). https://doi.org/10.3389/fnins.2014.00047
Herrera-Marschitz M, Perez-Lobos R, Lespay-Rebolledo C, Tapia-Bustos A, Casanova-Ortiz E, Morales P, Valdes JL, Bustamante D, Cassels BK (2018) Targeting sentinel proteins and extrasynaptic glutamate receptors: a therapeutic strategy for preventing the effects elicited by perinatal asphyxia? Neurotox Res 33(2):461–473. https://doi.org/10.1007/s12640-017-9795-9
Hertz L, Zielke HR (2004) Astrocytic control of glutamatergic activity: astrocytes as stars of the show. Trends Neurosci 27(12):735–743. https://doi.org/10.1016/j.tins.2004.10.008
Houtkooper RH, Cantó C, Wanders RJ, Auwerx J (2010) The secret life of NAD+: an old metabolite controlling new metabolic signaling pathways. Endocr Rev 31(2):194–223. https://doi.org/10.1210/er.2009-0026
Kamat JP, Devasagayam TP (1999) Nicotinamide (vitamin B3) as an effective antioxidant against oxidative damage in rat brain mitochondria. Redox Rep 4(4):179–184. https://doi.org/10.1179/135100099101534882
Kawamura T, Mori N, Shibata K (2016) β-nicotinamide mononucleotide, and anti-aging candidate compound, is retained in the body for longer than nicotinamide in rats. J Nutr Sci Vitaminol 62:272–276. https://doi.org/10.3177/jnsv.62.272
Kinouchi H, Kamii H, Mikawa S, Epstein CJ, Yoshimoto T, Chan PH (1998) Role of superoxide dismutase in ischemic brain injury: a study using SOD-1 transgenic mice. Cell Mol Neurobiol 18(6):609–620. https://doi.org/10.1023/A:1020677701368
Kleikers PW, Wingler K, Hermans JJ, Diebold I, Altenhöfer S, Radermacher KA, Janssen B, Görlach A, Schmidt HH (2012) NADPH oxidases as a source of oxidative stress and molecular target in ischemia/reperfusion injury. J Mol Med (Berl) 90(12):1391–1406. https://doi.org/10.1007/s00109-012-0963-3
Kuehne A, Emmert H, Soehle J, Winnefeld M, Fischer F, Wenck H, Gallinat S, Terstegen L, Lucius R, Hildebrand J, Zamboni N (2015) Acute activation of oxidative pentose phosphate pathway as first-line response to oxidative stress in human skin cells. Mol Cell 59(3):359–371. https://doi.org/10.1016/j.molcel.2015.06.017
Labudova O, Schuller E, Yeghiazaryan K, Kitzmueller E, Hoeger H, Lubec G, Lubec B (1999) Genes involved in the pathophysiology of perinatal asphyxia. Life Sci 64:1831–1838. https://doi.org/10.1016/S0024-3205(99)00125-3
Lardinois OM, Mestdagh MM, Rouxhet PG (1996) Reversible inhibition and irreversible inactivation of catalase in presence of hydrogen peroxide. BiochimBiophysActa. 1295(2):222–238. https://doi.org/10.1016/0167-4838(96)00043-X
Leaw B, Nair S, Lim R, Thornton C, Mallard C, Hagberg H (2017) Mitochondria, bioenergetics and excitotoxicity: new therapeutic targets in perinatal brain injury. Front Cell Neurosci 11(199). https://doi.org/10.3389/fncel.2017.00199
Lespay-Rebolledo C, Perez-Lobos R, Tapia-Bustos A, Vio V, Morales P, Herrera-Marschitz M (2018) Regionally impaired redox homeostasis in the brain of rats subjected to global perinatal asphyxia: sustained effect up to 14 postnatal days. Neurotox Res 34(3):660–676. https://doi.org/10.1007/s12640-018-9928-9
Li M, Sun M, Cao L, Gu JH, Ge J, Chen J, Han R, Qin YY, Zhou ZP, Ding Y, Qin ZH (2014) A TIGAR-regulated metabolic pathway is critical for protection of brain ischemia. J Neurosci 34(22):7458–7471. https://doi.org/10.1523/JNEUROSCI.4655-13.2014
Liu F, McCullough LD (2013) Inflammatory responses in hypoxic ischemic encephalopathy. Acta Pharmacol Sin 34(9):1121–1130. https://doi.org/10.1038/aps.2013.89
London RE (2015) The structural basis of XRCC1-mediated DNA repair. DNA Repair (Amst) 30:90–103. https://doi.org/10.1016/jdnarep.2015.02.005
Lu Q, Wainwright MS, Harris VA, Aggarwal S, Hou Y, Rau T, Poulsen DJ, Black SM (2012) Increased NADPH oxidase-derived superoxide is involved in the neuronal cell death induced by hypoxia-ischemia in neonatal hippocampal slice cultures. Free Radic Biol Med 53(5):1139–1151. https://doi.org/10.1016/j.freeradbiomed.2012.06.012
Lubec B, Labudova O, Hoeger H, Kirchner L, Lubec G (2002) Expression of transcription factors in the brain of rats with perinatal asphyxia. Biol Neonate 81:266–278. https://doi.org/10.1159/000056758
Lubos E, Loscalzo J, Handy DE (2011) Glutathione peroxidase-1 in health and disease: from molecular mechanisms to therapeutic opportunities. Antioxid Redox Signal 15:1957–1997. https://doi.org/10.1089/ars.2010.3586
Lushchak VI (2012) Glutathione homeostasis and functions: potential targets for medical interventions. J Amino Acids 2012(736837):1–26. https://doi.org/10.1155/2012/736837
Margis R, Dunand C, Teixeira FK, Margis-Pinheiro M (2008) Glutathione peroxidase family-an evolutionary overview. FEBS J 275:3959–3970. https://doi.org/10.1111/j.1742-4658.2008.06542.x
Marriott AL, Rojas-Mancilla E, Morales P, Herrera-Marschitz M, Tasker RA (2017) Models of progressive neurological dysfunction originating early in life. ProgNeurobiol 155:2–20. https://doi.org/10.1016/j.pneurobio.2015.10.001
Massudi H, Grant R, Guillemin GJ, Braidy N (2012) NAD+ metabolism and oxidative stress: the golden nucleotide on a crown of thorns. Redox Rep 17(1):28–46. https://doi.org/10.1179/1351000212Y.0000000001
Miyamoto Y, Koh YH, Park YS, Fujiwara N, Sakiyama H, Misonou Y, Ookawara T, Suzuki K, Honke K, Taniguchi N (2003) Oxidative stress caused by inactivation of glutathione peroxidase and adaptive responses. Biol Chem 384(4):567–574. https://doi.org/10.1515/BC.2003.064
Morales P, Reyes P, Klawitter V, Huaiquin P, Bustamante D, Fiedler JL, Herrera-Marschitz M (2005) Effects of perinatal asphyxia on cell proliferation and neuronal phenotype evaluated with organotypic hippocampal cultures. Neuroscience 135(2):421–431. https://doi.org/10.1016/j.neuroscience.2005.05.062
Morales P, Fiedler JL, Andres S, Berrios C, Huaiquin P, Bustamante D, Cardenas S, Parra E, Herrera-Marschitz M (2008) Plasticity of hippocampus following perinatal asphyxia: effects on postnatal apoptosis and neurogenesis. J Neurosci Res 86(12):2650–2662. https://doi.org/10.1002/jnr.21715
Morales P, Simola N, Bustamante D, Lisboa F, Fiedler J, Gebicke-Haerter P, Morelli M, Tasker RA, Herrera-Marschitz M (2010) Nicotinamide prevents the long-term effect of perinatal asphyxia on apoptosis, non-spatial working memory and anxiety in rats. Exp Brain Res 202(1):1–14. https://doi.org/10.1007/s00221-009-2103-z
Mosgoeller W, Kastner P, Fang-Kircher S, Kitzmueller E, Hoeger H, Sether P, Labudova O, Lubec G, Lubec B (2000) Brain RNA polymerase and nucleolar structure in perinatal asphyxia of the rat. ExpNeurol 161:174–182. https://doi.org/10.1006/exnr.1999.7232
Neira-Peña PE-M, Rojas-Mancilla E, Esmar D, Kraus C, Munoz V, Perez R, Rivera B, Bustamante D, Valdes JL, Hermoso M, Gebicke-Haerter P, Morales P, Herrera-Marschitz M (2014) Molecular, cellular, and behavioural effects produced by perinatal asphyxia: protection by poly (ADP-ribose) polymerase 1 (PARP-1) inhibition. In: Kostrzewa R (ed) Handbook of neurotoxicity. Springer, New York, pp 2075–2098. https://doi.org/10.1007/978-1-4614-5836-4_115
Neira-Peña T, Rojas-Mancilla E, Munoz-Vio V, Perez R, Gutierrez-Hernandez M, Bustamante D, Morales P, Hermoso MA, Gebicke-Haerter P, Herrera-Marschitz M (2015) Perinatal asphyxia leads to PARP-1 overactivity, p65 translocation, IL-1β and TNF-α overexpression, and apoptotic-like cell death in mesencephalon of neonatal rats: prevention by systemic neonatal nicotinamide administration. Neurotox Res 27(4):453–465. https://doi.org/10.1007/s12640-015-9517-0
Németh I, Boda D (1989) The ratio of oxidized/reduced glutathione as an index of oxidative stress in various experimental models of shock syndrome. Biomed Biochim Acta 48(2–3):S53–S57
Neumar RW, Meng FH, Mills AM, Xu YA, Zhang C, Welsh FA, Siman R (2001) Calpain activity in the rat brain after transient forebrain ischemia. Exp Neurol 170(1):27–35. https://doi.org/10.1006/exnr.2001.7708
Neumar RW, Xu YA, Gada H, Guttmann RP, Siman R (2003) Cross-talk between calpain and caspase proteolytic systems during neuronal apoptosis. J Biol Chem 278(16):14162–14167. https://doi.org/10.1074/jbc.M212255200
Okar DA, Manzano A, Navarro-Sabatè A, Riera L, Bartrons R, Lange AJ (2001) PFK-2/FBPase-2: maker and breaker of the essential biofactor fructose-2, 6-bisphosphate. Trends Biochem Sci 26(1):30–35. https://doi.org/10.1016/S0968-0004(00)01699-6
Ostwald K, Hagberg H, Andiné P, Karlsson JO (1993) Upregulation of calpain activity in neonatal rat brain after hypoxic-ischemia. Brain Res 630(1–2):289–294. https://doi.org/10.1016/0006-8993(93)90668-D
Poljsak B, Milisav I (2016) NAD+ as the link between oxidative stress, inflammation, caloric restriction, exercise, DNA repair, longevity, and health span. Rejuvenation Res 19(5):406–415. https://doi.org/10.1089/rej.2015.1767
Ramos-Martinez JI (2017) The regulation of the pentose phosphate pathway: remember Krebs. Arch Biochem Biophys 614:50e52. https://doi.org/10.1016/j.abb.2016.12.012–50e52
Ros S, Schulze A (2013) Balancing glycolytic flux: the role of 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatases in cancer metabolism. Cancer Metab 1(1):8. https://doi.org/10.1186/2049-3002-1-8
Rosenblat M, Aviram M (1998) Macrophage glutathione content and glutathione preoxidase activity are inversely related to cell mediated oxidation of LDL: in vitro and in vivo studies. Free Radic Biol Med 24:305–307. https://doi.org/10.1016/S0891-5849(97)00231-1
Seidl R, Stoeckler-Ipsiroglu S, Rolinski B, Kohlhauser C, Herkner KR, Lubec B, Lubec G (2000) Energy metabolism in graded perinatal asphyxia of the rat. Life Sci 67:421–435. https://doi.org/10.1016/S0024-3205(00)00630-5
Shan X, Aw TY, Jones DP (1990) Glutathione-dependent protection against oxidative injury. Pharmac Ther 47:61–71. https://doi.org/10.1016/0163-7258(90)90045-4
Sokolova T, Gutterer JM, Hirrlinger J, Hamprecht B, Dringen R (2001) Catalase in astroglia-rich primary cultures from rat brain: immunocytochemical localization and inactivation during the disposal of hydrogen peroxide. Neurosci Lett 297(2):129–132. https://doi.org/10.1016/S0304-3940(00)01689-X
Stincone A, Prigione A, Cramer T, Wamelink MM, Campbell K, Cheung E, Olin-Sandoval V, Grüning NM, Krüger A, TauqeerAlam M, Keller MA, Breitenbach M, Brindle KM, Rabinowitz JD, Ralser M (2015) The return of metabolism: biochemistry and physiology of the pentose phosphate pathway. Biol Rev Camb Philos Soc 90(3):927–963. https://doi.org/10.1111/brv.12140
Suh SW, Shin BS, Ma H, Van Hoecke M, Brennan AM, Yenari MA, Swanson RA (2008) Glucose and NADPH oxidase drive neuronal superoxide formation in stroke. Ann Neurol 64(6):654–663. https://doi.org/10.1002/ana.21511
Swarte R, Lequin M, Cherian P, Zecic A, van Goudoever J, Govaert P (2009) Imaging patterns of brain injury in term-birth asphyxia. Acta Paediatr 98(3):586–592. https://doi.org/10.1111/j.1651-2227.2008.01156.x
Taylor SC, Posch A (2014) The design of a quantitative western blot experiment. Biomed Res Int 2014:361590. https://doi.org/10.1155/2014/361590
Turunc Bayrakdar E, Uyanikgil Y, Kanit L, Koylu E, Yalcin A (2014) Nicotinamide treatment reduces the levels of oxidative stress, apoptosis, and PARP-1 activity in A b (1– 42)-induced rat model of Alzheimer’s disease. Free Radic Res 48(2):146–158. https://doi.org/10.3109/10715762.2013.857018
Vio V, Riveros AL, Tapia-Bustos A, Lespay-Rebolledo C, Perez-Lobos R, Muñoz L, Pismante P, Morales P, Araya E, Hassan N, Herrera-Marschitz M, Kogan MJ (2018) Gold nanorods/siRNA complex administration for knockdown of PARP-1: a potential treatment for perinatal asphyxia. Int J Nanomedicine 13:6839–6854. https://doi.org/10.2147/IJN.S175076
Wang S-N, Xu T-Y, Li W-L, Miao C-Y (2016) Targeting nicotinamide phosphoribosyltransferase as a potential therapeutic strategy to restore adult neurogenesis. CNS Neuroscience & Theraputics 22:431–439. https://doi.org/10.1111/cns.12539
Wei L, Nakajima S, Hsieh CL, Kanno S, Masutani M, Levine AS, Yasui A, Lan L (2013) Damage response of XRCC1 at sites of DNA single strand breaks is regulated by phosphorylation and ubiquitylation after degradation of poly(ADP-ribose). J Cell Sci 126(Pt 19):4414–4423. https://doi.org/10.1242/jcs.128272
Yamada KH, Kozlowski DA, Seidl SE, Lance S, Wieschhaus AJ, Sundivakkam P, Tiruppathi C, Chishti I, Herman IM, Kuchay SM, Chishti AH (2012) Targeted gene inactivation of calpain-1 suppresses cortical degeneration due to traumatic brain injury and neuronal apoptosis induced by oxidative stress. J Biol Chem 287(16):13182–13193. https://doi.org/10.1074/jbc.M111.302612
Zhang H, Ryu D, Wu Y, Gariani K, Wang X, Luan P, D’Amico D, Ropellr ER, Lutolf MP, Aebersold R, Schoonjans K, Menzies KJ, Anwerx J (2016) NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice. Science 352:1436–1443. https://doi.org/10.1126/science.aaf2693
Zhu H, Itoh K, Yamamoto M, Zweier JL, Li Y (2005) Role of Nrf2 signaling in regulation of antioxidants and phase 2 enzymes in cardiac fibroblasts: protection against reactive oxygen and nitrogen species-induced cell injury. FEBS Lett 579(14):3029–3036
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Contract grant sponsors: FONDECYT-Chile (no. 1120079, MHM; 1180042, YI, PMR, MHM; 1190562, PMR). CONICYT Operational Support no. 21140281 (LRC) and no. 21151232 (TBA). CONICYT-Chile fellowships: no. 21140281 (LRC) and no. 21151232 (TBA).
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All procedures were conducted in accordance with the animal care and use protocol established by a Local Ethics Committee for experimentation with laboratory animals at the Medical Faculty, University of Chile (Protocol CBA no. 0722 FMUCH) and by an ad hoc commission of the Chilean Council for Science and Technology Research (CONICYT), endorsing the principles of laboratory animal care (NIH; No. 86-23; revised 1985). Animals were permanently monitored (on 24 h basis) regarding well being, following the ARRIVE guidelines for reporting animal studies (www.nc3rs.org.uk/ARRIVE).
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Lespay-Rebolledo, C., Tapia-Bustos, A., Bustamante, D. et al. The Long-Term Impairment in Redox Homeostasis Observed in the Hippocampus of Rats Subjected to Global Perinatal Asphyxia (PA) Implies Changes in Glutathione-Dependent Antioxidant Enzymes and TIGAR-Dependent Shift Towards the Pentose Phosphate Pathways: Effect of Nicotinamide. Neurotox Res 36, 472–490 (2019). https://doi.org/10.1007/s12640-019-00064-4
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DOI: https://doi.org/10.1007/s12640-019-00064-4