Endogenous Neuroprotective Mechanism of ATP2B1 in Transcriptional Regulation of Ischemic Preconditioning

Overview

Journal Am J Transl Res

Specialty General Medicine

Date 2021 Apr 12

PMID 33841647

Citations 2

Authors

Jinggui Gao

Zhenxiu Qin

Xiang Qu

Shuang Wu

Xiaoyun Xie

Chengwei Liang

Jingli Liu

Affiliations

Soon will be listed here.

Abstract

Methods: Using transcriptome method, we sequenced the serum of 3 stroke patients with progenitor TIA and 3 stroke patients without prodromal TIA. We explored the expression profiles of miRNAs and mRNAs in response to IPC, and predicted the regulatory pathway of IPC related genes and their expression in cerebral neurons. The methylation consistent expression of IPC-related gene ATP2B1 in blood and brain and alternative polyadenylate (APA) analysis were used to identify the pathway and molecular mechanism of endogenous neuroprotection of IPC.

Results: We found that the brain protective effect of IPC was related to platelet homeostasis and Ca concentration. IPC-related gene ATP2B1 was highly expressed in γ-aminobutyric acid (GABA)-containing neurons in the brain. From the mechanism, we speculated that ATP2B1 was representative of the same methylation in blood and brain and was affected by alternative polyadenylation.

Conclusion: We speculate that IPC can induce alternative polyadenylation of ATP2B1 and trigger the mechanism of brain endogenous neuroprotection by regulating the decrease of Ca concentration in platelet homeostasis pathway and the activation of GABAB receptor.

Citing Articles

Preconditioning With Intermittent Hypobaric Hypoxia Attenuates Stroke Damage and Modulates Endocytosis in Residual Neurons.

Wan Y, Huang L, Liu Y, Ji W, Li C, Ge R Front Neurol. 2022; 12:750908.

PMID: 34975719 PMC: 8715922. DOI: 10.3389/fneur.2021.750908.

Ischemic Stroke and Sleep: The Linking Genetic Factors.

Korostovtseva L Cardiol Ther. 2021; 10(2):349-375.

PMID: 34191267 PMC: 8555086. DOI: 10.1007/s40119-021-00231-9.

References

Ding S . Ca(2+) signaling in astrocytes and its role in ischemic stroke. Adv Neurobiol. 2014; 11:189-211. PMC: 4454286. DOI: 10.1007/978-3-319-08894-5_10. View

Shao J, Zhang J, Zhang Z, Jiang H, Lou X, Huang B . Alternative polyadenylation in glioblastoma multiforme and changes in predicted RNA binding protein profiles. OMICS. 2013; 17(3):136-49. PMC: 3603499. DOI: 10.1089/omi.2012.0098. View

Sommer C . Neuronal plasticity after ischemic preconditioning and TIA-like preconditioning ischemic periods. Acta Neuropathol. 2008; 117(5):511-23. DOI: 10.1007/s00401-008-0473-0. View

Di Leva F, Domi T, Fedrizzi L, Lim D, Carafoli E . The plasma membrane Ca2+ ATPase of animal cells: structure, function and regulation. Arch Biochem Biophys. 2008; 476(1):65-74. DOI: 10.1016/j.abb.2008.02.026. View

Dhodda V, Sailor K, Bowen K, Vemuganti R . Putative endogenous mediators of preconditioning-induced ischemic tolerance in rat brain identified by genomic and proteomic analysis. J Neurochem. 2004; 89(1):73-89. DOI: 10.1111/j.1471-4159.2004.02316.x. View

Zhou G, Soufan O, Ewald J, Hancock R, Basu N, Xia J . NetworkAnalyst 3.0: a visual analytics platform for comprehensive gene expression profiling and meta-analysis. Nucleic Acids Res. 2019; 47(W1):W234-W241. PMC: 6602507. DOI: 10.1093/nar/gkz240. View

Schaller B . Ischemic preconditioning as induction of ischemic tolerance after transient ischemic attacks in human brain: its clinical relevance. Neurosci Lett. 2005; 377(3):206-11. DOI: 10.1016/j.neulet.2004.12.004. View

Casas A, Kleikers P, Geuss E, Langhauser F, Adler T, Busch D . Calcium-dependent blood-brain barrier breakdown by NOX5 limits postreperfusion benefit in stroke. J Clin Invest. 2019; 129(4):1772-1778. PMC: 6436900. DOI: 10.1172/JCI124283. View

Murry C, Jennings R, Reimer K . Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation. 1986; 74(5):1124-36. DOI: 10.1161/01.cir.74.5.1124. View

10.

Hodge R, Bakken T, Miller J, Smith K, Barkan E, Graybuck L . Conserved cell types with divergent features in human versus mouse cortex. Nature. 2019; 573(7772):61-68. PMC: 6919571. DOI: 10.1038/s41586-019-1506-7. View

11.

Zsuga J, Gesztelyi R, Juhasz B, Kemeny-Beke A, Fekete I, Csiba L . Prior transient ischemic attack is independently associated with lesser in-hospital case fatality in acute stroke. Psychiatry Clin Neurosci. 2008; 62(6):705-12. DOI: 10.1111/j.1440-1819.2008.01874.x. View

12.

Xia Z, Donehower L, Cooper T, Neilson J, Wheeler D, Wagner E . Dynamic analyses of alternative polyadenylation from RNA-seq reveal a 3'-UTR landscape across seven tumour types. Nat Commun. 2014; 5:5274. PMC: 4467577. DOI: 10.1038/ncomms6274. View

13.

Pignataro G, Brancaccio P, Laudati G, Valsecchi V, Anzilotti S, Casamassa A . Sodium/calcium exchanger as main effector of endogenous neuroprotection elicited by ischemic tolerance. Cell Calcium. 2020; 87:102183. DOI: 10.1016/j.ceca.2020.102183. View

14.

Phillis J, Perkins L, ORegan M . Characterization of glutamate, aspartate, and GABA release from ischemic rat cerebral cortex. Brain Res Bull. 1994; 34(5):457-66. DOI: 10.1016/0361-9230(94)90019-1. View

15.

Yang T, Li Q, Zhang F . Regulation of gene expression in ischemic preconditioning in the brain. Cond Med. 2018; 1(1):47-56. PMC: 6051752. View

16.

Koupenova M, Kehrel B, Corkrey H, Freedman J . Thrombosis and platelets: an update. Eur Heart J. 2017; 38(11):785-791. PMC: 11110018. DOI: 10.1093/eurheartj/ehw550. View

17.

Elkon R, Ugalde A, Agami R . Alternative cleavage and polyadenylation: extent, regulation and function. Nat Rev Genet. 2013; 14(7):496-506. DOI: 10.1038/nrg3482. View

18.

Hong W, Ruan H, Zhang Z, Ye Y, Liu Y, Li S . APAatlas: decoding alternative polyadenylation across human tissues. Nucleic Acids Res. 2019; 48(D1):D34-D39. PMC: 6943053. DOI: 10.1093/nar/gkz876. View

19.

Stevens S, Vartanian K, Stenzel-Poore M . Reprogramming the response to stroke by preconditioning. Stroke. 2014; 45(8):2527-31. PMC: 4240276. DOI: 10.1161/STROKEAHA.114.002879. View

20.

Koupenova M, Clancy L, Corkrey H, Freedman J . Circulating Platelets as Mediators of Immunity, Inflammation, and Thrombosis. Circ Res. 2018; 122(2):337-351. PMC: 5777300. DOI: 10.1161/CIRCRESAHA.117.310795. View