Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 1.736
5-Year Impact Factor – 2.135
Index Copernicus  – 168.52
MEiN – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

Ahead of print

doi: 10.17219/acem/157477

Publication type: original article

Language: English

License: Creative Commons Attribution 3.0 Unported (CC BY 3.0)

Download citation:

  • BIBTEX (JabRef, Mendeley)
  • RIS (Papers, Reference Manager, RefWorks, Zotero)

Cite as:


Wei Z, Wu R, Zhang L, Xu P. ATPIF1 alleviates oxygen glucose deprivation/reoxygenation-induced astrocyte injury in vitro: A rat model of ischemic brain injury [published online as ahead of print on March 7, 2023]. Adv Clin Exp Med. 2023. doi:10.17219/acem/157477

ATPIF1 alleviates oxygen glucose deprivation/reoxygenation-induced astrocyte injury in vitro: A rat model of ischemic brain injury

Zhijie Wei1,2,A,B,C,D,F, Rui Wu2,A,B,C,F, Li Zhang2,A,B,C,F, Ping Xu2,A,C,E,F

1 Department of Neurology, Soochow University, China

2 Department of Neurology, Affiliated Hospital of Zunyi Medical University, China

Abstract

Background. The role of ATPIF1 in ischemic brain injury is rarely reported.
Objectives. This study explored the effect of ATPIF1 on astrocyte activity under oxygen glucose deprivation/reoxygenation (OGD/R).
Material and Methods. The study sample was randomly allocated into: 1) control group (blank control); 2) OGD/R group (hypoxia for 6 h/reoxygenation for 1 h); 3) siRNA negative control (NC) group (OGD/R model+siRNA NC); and 4) siRNA-ATPIF1 group (OGD/R model+siRNA-ATPIF1). The OGD/R cell model was established from Sprague Dawley (SD) rats to simulate ischemia/reperfusion injury. Cells in the siRNA-ATPIF1 group were treated with siATPIF1. Ultrastructural changes in the mitochondria were observed using transmission electron microscopy (TEM). Apoptosis, cell cycle, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) were detected with flow cytometry. The protein expression levels of nuclear factor kappa B (NF-κB), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X (Bax), and caspase-3 were detected with western blot.
Results. In the model group, the cell structure and the ridge structure were destroyed, and mitochondria edema, outer membrane damage and vacuole-like lesions were observed. Compared with the control group, the OGD/R group had considerably increased apoptosis, G0/G1 phase, ROS content, MMP, and Bax, caspase-3 and NF-κB protein expression, as well as markedly decreased S phase and Bcl-2 protein expression. Compared with the OGD/R group, the siRNA-ATPIF1 group had considerably decreased apoptosis, G0/G1 phase, ROS content, MMP, and Bax, caspase-3 and NF-κB protein expression, as well as remarkably increased S phase and Bcl-2 protein expression.
Conclusion. The inhibition of ATPIF1 may alleviate OGD/R-induced astrocyte injury by regulating the NF-κB signaling pathway, inhibiting apoptosis, and reducing the ROS content and MMP in the rat brain ischemic model.

Key words

apoptosis, NF-κB signaling pathway, OGD/R, astrocytes, ATPIF1

Graphical abstract


Graphical abstracts

References (31)

  1. Radak D, Katsiki N, Resanovic I, et al. Apoptosis and acute brain ischemia in ischemic stroke. Curr Vasc Pharmacol. 2017;15(2):115–122. doi:10.2174/1570161115666161104095522
  2. Feigin VL, Krishnamurthi RV, Parmar P, et al. Update on the global burden of ischemic and hemorrhagic stroke in 1990–2013: The GBD 2013 Study. Neuroepidemiology. 2015;45(3):161–176. doi:10.1159/000441085
  3. Avan A, Hachinski V. Stroke and dementia, leading causes of neurological disability and death, potential for prevention. Alzheimers Dementia. 2021;17(6):1072–1076. doi:10.1002/alz.12340
  4. Wang J, Sareddy GR, Lu Y, et al. Astrocyte-derived estrogen regulates reactive astrogliosis and is neuroprotective following ischemic brain injury. J Neurosci. 2020;40(50):9751–9771. doi:10.1523/JNEUROSCI.0888-20.2020
  5. Rossi DJ, Brady JD, Mohr C. Astrocyte metabolism and signaling during brain ischemia. Nat Neurosci. 2007;10(11):1377–1386. doi:10.1038/nn2004
  6. van Putten MJAM, Fahlke C, Kafitz KW, Hofmeijer J, Rose CR. Dysregulation of astrocyte ion homeostasis and its relevance for stroke-induced brain damage. Int J Mol Sci. 2021;22(11):5679. doi:10.3390/ijms22115679
  7. Kandul NP, Zhang T, Hay BA, Guo M. Selective removal of deletion-bearing mitochondrial DNA in heteroplasmic Drosophila. Nat Commun. 2016;7(1):13100. doi:10.1038/ncomms13100
  8. Martín-Jiménez R, Faccenda D, Allen E, et al. Reduction of the ATPase inhibitory factor 1 (IF1) leads to visual impairment in vertebrates. Cell Death Dis. 2018;9(6):669. doi:10.1038/s41419-018-0578-x
  9. Li J, Sun YBY, Chen W, et al. Smad4 promotes diabetic nephropathy by modulating glycolysis and OXPHOS. EMBO Rep. 2020;21(2):e48781. doi:10.15252/embr.201948781
  10. Chen WW, Birsoy K, Mihaylova MM, et al. Inhibition of ATPIF1 ameliorates severe mitochondrial respiratory chain dysfunction in mammalian cells. Cell Rep. 2014;7(1):27–34. doi:10.1016/j.celrep.2014.02.046
  11. Kurbasic E, Sjöström M, Krogh M, et al. Changes in glycoprotein expression between primary breast tumour and synchronous lymph node metastases or asynchronous distant metastases. Clin Proteom. 2015;12(1):13. doi:10.1186/s12014-015-9084-7
  12. Shah DI, Takahashi-Makise N, Cooney JD, et al. Mitochondrial Atpif1 regulates haem synthesis in developing erythroblasts. Nature. 2012;491(7425):608–612. doi:10.1038/nature11536
  13. Mu W, Cheng X, Zhang X, et al. Hinokiflavone induces apoptosis via activating mitochondrial ROS/JNK/caspase pathway and inhibiting NF‐κB activity in hepatocellular carcinoma. J Cell Mol Med. 2020;24(14):8151–8165. doi:10.1111/jcmm.15474
  14. Wang X, Lu X, Zhu R, et al. Betulinic acid induces apoptosis in differentiated PC12 cells via ROS-mediated mitochondrial pathway. Neurochem Res. 2017;42(4):1130–1140. doi:10.1007/s11064-016-2147-y
  15. Zhang T, Zhao G, Zhu X, et al. Sodium selenite induces apoptosis via ROS‐mediated NF‐κB signaling and activation of the Bax–caspase‐9–caspase‐3 axis in 4T1 cells. J Cell Physiol. 2019;234(3):2511–2522. doi:10.1002/jcp.26783
  16. Yamagata K. Astrocyte‐induced synapse formation and ischemic stroke. J Neurosci Res. 2021;99(5):1401–1413. doi:10.1002/jnr.24807
  17. Santello M, Toni N, Volterra A. Astrocyte function from information processing to cognition and cognitive impairment. Nat Neurosci. 2019;22(2):154–166. doi:10.1038/s41593-018-0325-8
  18. Bayraktar OA, Bartels T, Holmqvist S, et al. Astrocyte layers in the mammalian cerebral cortex revealed by a single-cell in situ transcriptomic map. Nat Neurosci. 2020;23(4):500–509. doi:10.1038/s41593-020-0602-1
  19. Zamboni M, Llorens-Bobadilla E, Magnusson JP, Frisén J. A widespread neurogenic potential of neocortical astrocytes is induced by injury. Cell Stem Cell. 2020;27(4):605–617.e5. doi:10.1016/j.stem.2020.07.006
  20. Wang K, Chen H, Zhou Z, Zhang H, Zhou HJ, Min W. ATPIF1 maintains normal mitochondrial structure which is impaired by CCM3 deficiency in endothelial cells. Cell Biosci. 2021;11(1):11. doi:10.1186/s13578-020-00514-z
  21. Faccenda D, Tan CH, Seraphim A, Duchen MR, Campanella M. IF1 limits the apoptotic-signalling cascade by preventing mitochondrial remodelling. Cell Death Differ. 2013;20(5):686–697. doi:10.1038/cdd.2012.163
  22. Uzdensky AB. Apoptosis regulation in the penumbra after ischemic stroke: Expression of pro- and antiapoptotic proteins. Apoptosis. 2019;24(9–10):687–702. doi:10.1007/s10495-019-01556-6
  23. Li M, Tan J, Miao Y, Lei P, Zhang Q. The dual role of autophagy under hypoxia-involvement of interaction between autophagy and apoptosis. Apoptosis. 2015;20(6):769–777. doi:10.1007/s10495-015-1110-8
  24. Xu Y, Gao G, Sun X, Liu Q, Li C. ATPase inhibitory factor 1 is critical for regulating sevoflurane-induced microglial inflammatory responses and caspase-3 activation. Front Cell Neurosci. 2021;15:770666. doi:10.3389/fncel.2021.770666
  25. Clavier A, Rincheval-Arnold A, Colin J, Mignotte B, Guénal I. Apoptosis in Drosophila: Which role for mitochondria? Apoptosis. 2016;21(3):239–251. doi:10.1007/s10495-015-1209-y
  26. Soond SM, Kozhevnikova MV, Savvateeva LV, Townsend PA, Zamyatnin AA. Intrinsically connected: Therapeutically targeting the cathepsin proteases and the Bcl-2 family of protein substrates as co-regulators of apoptosis. Int J Mol Sci. 2021;22(9):4669. doi:10.3390/ijms22094669
  27. Khan H, Ullah H, Castilho PCMF, et al. Targeting NF-κB signaling pathway in cancer by dietary polyphenols. Crit Rev Food Sci Nutr. 2020;60(16):2790–2800. doi:10.1080/10408398.2019.1661827
  28. Soleimani A, Rahmani F, Ferns GA, Ryzhikov M, Avan A, Hassanian SM. Role of the NF-κB signaling pathway in the pathogenesis of colorectal cancer. Gene. 2020;726:144132. doi:10.1016/j.gene.2019.144132
  29. Kandasamy M. NF-κB signalling as a pharmacological target in COVID-19: Potential roles for IKKβ inhibitors. Naunyn Schmiedeberg’s Arch Pharmacol. 2021;394(3):561–567. doi:10.1007/s00210-020-02035-5
  30. Shen M, Hu Y, Yang Y, et al. Betulinic acid induces ROS-dependent apoptosis and S-phase arrest by inhibiting the NF-κ B pathway in human multiple myeloma. Oxid Med Cell Longev. 2019;2019:5083158. doi:10.1155/2019/5083158
  31. Cabezón E, Butler PJG, Runswick MJ, Carbajo RJ, Walker JE. Homologous and heterologous inhibitory effects of ATPase inhibitor proteins on F-ATPases. J Biol Chem. 2002;277(44):41334–41341. doi:10.1074/jbc.M207169200