COX5A Over-expression Protects Cortical Neurons from Hypoxic Ischemic Injury in Neonatal Rats Associated with TPI Up-regulation

Overview

Journal BMC Neurosci

Publisher Biomed Central

Specialty Neurology

Date 2020 May 1

PMID 32349668

Citations 12

Authors

Ya Jiang

Xue Bai

Ting-Ting Li

Mohammed Al-Hawwas

Yuan Jin

Yu Zou

Yue Hu

Lin-Yi Liu

Ying Zhang

Qing Liu

Hao Yang

Jun Ma

Ting-Hua Wang

Jia Liu

Liu-Lin Xiong

Affiliations

Soon will be listed here.

Abstract

Background: Neonatal hypoxic-ischemic encephalopathy (HIE) represents as a major cause of neonatal morbidity and mortality. However, the underlying molecular mechanisms in brain damage are still not fully elucidated. This study was conducted to determine the specific potential molecular mechanism in the hypoxic-ischemic induced cerebral injury.

Methods: Here, hypoxic-ischemic (HI) animal models were established and primary cortical neurons were subjected to oxygen-glucose deprivation (OGD) to mimic HIE model in vivo and in vitro. The HI-induced neurological injury was evaluated by Zea-longa scores, Triphenyte-trazoliumchloride (TTC) staining the Terminal Deoxynucleotidyl Transferased Utp Nick End Labeling (TUNEL) and immunofluorescent staining. Then the expression of Cytochrome c oxidase subunit 5a (COX5A) was determined by immunohistochemistry, western blotting (WB) and quantitative real time Polymerase Chain Reaction (qRT-PCR) techniques. Moreover, HSV-mediated COX5A over-expression virus was transducted into OGD neurons to explore the role of COX5A in vitro, and the underlying mechanism was predicted by GeneMANIA, then verified by WB and qRT-PCR.

Results: HI induced a severe neurological dysfunction, brain infarction, and cell apoptosis as well as obvious neuron loss in neonatal rats, in corresponding to the decrease on the expression of COX5A in both sides of the brain. What's more, COX5A over-expression significantly promoted the neuronal survival, reduced the apoptosis rate, and markedly increased the neurites length after OGD. Moreover, Triosephosephate isomerase (TPI) was predicted as physical interactions with COX5A, and COX5A over-expression largely increased the expressional level of TPI.

Conclusions: The present findings suggest that COX5A plays an important role in promoting neurological recovery after HI, and this process is related to TPI up-regulation.

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References

Xiyang Y, Wang Y, Zhao Y, Ru J, Lu B, Zhang Y . Sodium Channel Voltage-Gated Beta 2 Plays a Vital Role in Brain Aging Associated with Synaptic Plasticity and Expression of COX5A and FGF-2. Mol Neurobiol. 2015; 53(2):955-967. DOI: 10.1007/s12035-014-9048-3. View

Clancy B, Darlington R, Finlay B . Translating developmental time across mammalian species. Neuroscience. 2001; 105(1):7-17. DOI: 10.1016/s0306-4522(01)00171-3. View

Zarifi M, Astrakas L, Poussaint T, Plessis Ad A, Zurakowski D, Tzika A . Prediction of adverse outcome with cerebral lactate level and apparent diffusion coefficient in infants with perinatal asphyxia. Radiology. 2002; 225(3):859-70. DOI: 10.1148/radiol.2253011797. View

Callahan L, Supinski G . Downregulation of diaphragm electron transport chain and glycolytic enzyme gene expression in sepsis. J Appl Physiol (1985). 2005; 99(3):1120-6. DOI: 10.1152/japplphysiol.01157.2004. View

Wei L, Wang J, Cao Y, Ren Q, Zhao L, Li X . Hyperbaric oxygenation promotes neural stem cell proliferation and protects the learning and memory ability in neonatal hypoxic-ischemic brain damage. Int J Clin Exp Pathol. 2015; 8(2):1752-9. PMC: 4396307. View

Kim C, Lim Y, Yoo B, Won N, Kim S, Kim G . Regulation of post-translational protein arginine methylation during HeLa cell cycle. Biochim Biophys Acta. 2010; 1800(9):977-85. DOI: 10.1016/j.bbagen.2010.06.004. View

Yildiz E, Ekici B, Tatli B . Neonatal hypoxic ischemic encephalopathy: an update on disease pathogenesis and treatment. Expert Rev Neurother. 2016; 17(5):449-459. DOI: 10.1080/14737175.2017.1259567. View

Ashwal S, Tone B, Tian H, Chong S, Obenaus A . Comparison of two neonatal ischemic injury models using magnetic resonance imaging. Pediatr Res. 2007; 61(1):9-14. DOI: 10.1203/01.pdr.0000251612.16069.4b. View

Doycheva D, Shih G, Chen H, Applegate R, Zhang J, Tang J . Granulocyte-colony stimulating factor in combination with stem cell factor confers greater neuroprotection after hypoxic-ischemic brain damage in the neonatal rats than a solitary treatment. Transl Stroke Res. 2013; 4(2):171-8. PMC: 3615723. DOI: 10.1007/s12975-012-0225-2. View

10.

Dixon B, Reis C, Ho W, Tang J, Zhang J . Neuroprotective Strategies after Neonatal Hypoxic Ischemic Encephalopathy. Int J Mol Sci. 2015; 16(9):22368-401. PMC: 4613313. DOI: 10.3390/ijms160922368. View

11.

Dingley J, Tooley J, Porter H, Thoresen M . Xenon provides short-term neuroprotection in neonatal rats when administered after hypoxia-ischemia. Stroke. 2005; 37(2):501-6. DOI: 10.1161/01.STR.0000198867.31134.ac. View

12.

Racay P, Tatarkova Z, Drgova A, Kaplan P, Dobrota D . Ischemia-reperfusion induces inhibition of mitochondrial protein synthesis and cytochrome c oxidase activity in rat hippocampus. Physiol Res. 2008; 58(1):127-138. DOI: 10.33549/physiolres.931383. View

13.

Schmidt M, Marx T, Gloggl E, Reinelt H, Schirmer U . Xenon attenuates cerebral damage after ischemia in pigs. Anesthesiology. 2005; 102(5):929-36. DOI: 10.1097/00000542-200505000-00011. View

14.

Rousselet E, Kriz J, Seidah N . Mouse model of intraluminal MCAO: cerebral infarct evaluation by cresyl violet staining. J Vis Exp. 2012; (69). PMC: 3520579. DOI: 10.3791/4038. View

15.

Zhu C, Qiu L, Wang X, Hallin U, Cande C, Kroemer G . Involvement of apoptosis-inducing factor in neuronal death after hypoxia-ischemia in the neonatal rat brain. J Neurochem. 2003; 86(2):306-17. DOI: 10.1046/j.1471-4159.2003.01832.x. View

16.

Shankaran S . Therapeutic hypothermia for neonatal encephalopathy. Curr Treat Options Neurol. 2012; 14(6):608-19. PMC: 3519960. DOI: 10.1007/s11940-012-0200-y. View

17.

Kim H . Statistical notes for clinical researchers: Sample size calculation 3. Comparison of several means using one-way ANOVA. Restor Dent Endod. 2016; 41(3):231-4. PMC: 4977355. DOI: 10.5395/rde.2016.41.3.231. View

18.

Ongwijitwat S, Wong-Riley M . Is nuclear respiratory factor 2 a master transcriptional coordinator for all ten nuclear-encoded cytochrome c oxidase subunits in neurons?. Gene. 2005; 360(1):65-77. DOI: 10.1016/j.gene.2005.06.015. View

19.

Allen L, Zhao X, Caughey W, Poyton R . Isoforms of yeast cytochrome c oxidase subunit V affect the binuclear reaction center and alter the kinetics of interaction with the isoforms of yeast cytochrome c. J Biol Chem. 1995; 270(1):110-8. DOI: 10.1074/jbc.270.1.110. View

20.

Xiong L, Xue L, Jiang Y, Ma Z, Jin Y, Wang Y . Suppression of PDGF induces neuronal apoptosis after neonatal cerebral hypoxia and ischemia by inhibiting P-PI3K and P-AKT signaling pathways. Brain Res. 2019; 1719:77-88. DOI: 10.1016/j.brainres.2019.05.012. View