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Cited by 35Mitochondrial Function and PathologyNeurological Disorders and TreatmentsHeat shock proteins research

Preserving mitochondrial function by inhibiting GRP75 ameliorates neuron injury under ischemic stroke.

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Wen, Bin, Xu, Kai, Huang, Rui, Jiang, Teng, Wang, Jian, Chen, Jiehui, Chen, Juan, He, Benhong·2022·Molecular Medicine Reports
DOI 10.3892/mmr.2022.12681PMC PMC8941507
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Abstract

Ischemic stroke is a life‑threatening disease, which is closely related to neuron damage during ischemia. Mitochondrial dysfunction is essentially involved in the pathophysiological process of ischemic stroke. Mitochondrial calcium overload contributes to the development of mitochondrial dysfunction. However, the underlying mechanisms of mitochondrial calcium overload are far from being fully revealed. In the present study, middle cerebral artery obstruction (MCAO) was performed in vivo and oxygen and glucose deprivation (OGD) in vitro. The results indicated that both MCAO and OGD induced significant mitochondrial dysfunction in vivo and in vitro. The mitochondria became fragmented under hypoxia conditions, accompanied with upregulation of the heat shock protein 75 kDa glucose‑regulated protein (GRP75). Inhibition of GRP75 was able to effectively ameliorate mitochondrial calcium overload and preserve mitochondrial function, which may provide evidence for further translational studies of ischemic diseases.

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  1. [1]Paul S Candelario-Jalil E Emerging neuroprotective strategies for the treatment of ischemic stroke: An overview of clinical and preclinical studies Exp Neurol 335 113518 2021 10.1016/j.expneurol.2020.113518 33144066 PMC7869696 · DOI
  2. [2]Su XT Wang L Ma SM Cao Y Yang NN Lin LL Fisher M Yang JW Liu CZ Mechanisms of acupuncture in the regulation of oxidative stress in treating ischemic stroke Oxid Med Cell Longev Oct 24 2020 (Epub ahead of print) 10.1155/2020/7875396 PMC7644298 33178387 · DOI
  3. [3]Ranjbar Taklimie F Gasterich N Scheld M Weiskirchen R Beyer C Clarner T Zendedel A Hypoxia induces astrocyte-derived Lipocalin-2 in ischemic stroke Int J Mol Sci 20 1271 2019 10.3390/ijms20061271 30871254 PMC6471434 · DOI
  4. [4]Lv J Guan W You Q Deng L Zhu Y Guo K Gao X Kong J Yang C RIPC provides neuroprotection against ischemic stroke by suppressing apoptosis via the mitochondrial pathway Sci Rep 10 5361 2020 10.1038/s41598-020-62336-w 32210331 PMC7093414 · DOI
  5. [5]Gao CL Hou GG Liu J Ru T Xu YZ Zhao SY Ye H Zhang LY Chen KX Guo YW Synthesis and target identification of benzoxepane derivatives as potential anti-neuroinflammatory agents for ischemic stroke Angew Chem Int Ed Engl 59 2429 2439 2020 10.1002/anie.201912489 31782597 · DOI
  6. [6]Alim I Caulfield JT Chen Y Swarup V Geschwind DH Ivanova E Seravalli J Ai Y Sansing LH Ste Marie EJ Selenium drives a transcriptional adaptive program to block ferroptosis and treat stroke Cell 177 1262 1279.e1225 2019 10.1016/j.cell.2019.03.032 31056284 · DOI
  7. [7]Guadagno JV Jones PS Fryer TD Barret O Aigbirhio FI Carpenter TA Price CJ Gillard JH Warburton EA Baron JC Local relationships between restricted water diffusion and oxygen consumption in the ischemic human brain Stroke 37 1741 1748 2006 10.1161/01.STR.0000232437.00621.86 16763173 · DOI
  8. [8]Li C Sun H Xu G McCarter KD Li J Mayhan WG Mito-tempo prevents nicotine-induced exacerbation of ischemic brain damage J Appl Physiol (1985) 125 49 57 2018 10.1152/japplphysiol.01084.2017 29420160 · DOI
  9. [9]Rose J Brian C Woods J Pappa A Panayiotidis MI Powers R Franco R Mitochondrial dysfunction in glial cells: Implications for neuronal homeostasis and survival Toxicology 391 109 115 2017 10.1016/j.tox.2017.06.011 28655545 PMC5681369 · DOI
  10. [10]Mondal NK Behera J Kelly KE George AK Tyagi PK Tyagi N Tetrahydrocurcumin epigenetically mitigates mitochondrial dysfunction in brain vasculature during ischemic stroke Neurochem Int 122 120 138 2019 10.1016/j.neuint.2018.11.015 30472160 PMC6666268 · DOI
  11. [11]Zhao D Sun Y Tan Y Zhang Z Hou Z Gao C Feng P Zhang X Yi W Gao F Short-duration swimming exercise after myocardial infarction attenuates cardiac dysfunction and regulates mitochondrial quality control in aged mice Oxid Med Cell Longev 2018 4079041 2018 10.1155/2018/4079041 29849892 PMC5925211 · DOI
  12. [12]Galvan DL Green NH Danesh FR The hallmarks of mitochondrial dysfunction in chronic kidney disease Kidney Int 92 1051 1057 2017 10.1016/j.kint.2017.05.034 28893420 PMC5667560 · DOI · Paper page
  13. [13]Thoudam T Ha CM Leem J Chanda D Park JS Kim HJ Jeon JH Choi YK Liangpunsakul S Huh YH PDK4 augments ER-mitochondria contact to dampen skeletal muscle insulin signaling during obesity Diabetes 68 571 586 2019 10.2337/db18-0363 30523025 PMC6385748 · DOI · Paper page
  14. [14]Jiang J Dai J Cui H Vitexin reverses the autophagy dysfunction to attenuate MCAO-induced cerebral ischemic stroke via mTOR/Ulk1 pathway Biomed Pharmacother 99 583 590 2018 10.1016/j.biopha.2018.01.067 29710456 · DOI
  15. [15]Smith HK Russell JM Granger DN Gavins FN Critical differences between two classical surgical approaches for middle cerebral artery occlusion-induced stroke in mice J Neurosci Methods 249 99 105 2015 10.1016/j.jneumeth.2015.04.008 25936850 · DOI
  16. [16]Zhang Y Liu X Bai J Tian X Zhao X Liu W Duan X Shang W Fan HY Tong C Mitoguardin regulates mitochondrial fusion through MitoPLD and is required for neuronal homeostasis Mol Cell 61 111 124 2016 10.1016/j.molcel.2015.11.017 26711011 · DOI · Paper page
  17. [17]Liang T Hang W Chen J Wu Y Wen B Xu K Ding B Chen J ApoE4 (Δ272-299) induces mitochondrial-associated membrane formation and mitochondrial impairment by enhancing GRP75-modulated mitochondrial calcium overload in neuron Cell Biosci 11 50 2021 10.1186/s13578-021-00563-y 33676568 PMC7937300 · DOI · Paper page
  18. [18]Knauss S Albrecht C Dirnagl U Mueller S Harms C Hoffmann CJ Koch SP Endres M Boehm-Sturm P A semiquantitative non-invasive measurement of PcomA patency in C57BL/6 mice explains variance in ischemic brain damage in filament MCAO Front Neurosci 14 576741 2020 10.3389/fnins.2020.576741 33071747 PMC7538613 · DOI
  19. [19]Seo SJ Yoon SH Do JT Mitochondrial dynamics in stem cells and differentiation Int J Mol Sci 19 3893 2018 10.3390/ijms19123893 30563106 PMC6321186 · DOI
  20. [20]Wu PK Hong SK Starenki D Oshima K Shao H Gestwicki JE Tsai S Park JI Mortalin/HSPA9 targeting selectively induces KRAS tumor cell death by perturbing mitochondrial membrane permeability Oncogene 39 4257 4270 2020 10.1038/s41388-020-1285-5 32291414 PMC7244387 · DOI
  21. [21]Rousaki A Miyata Y Jinwal UK Dickey CA Gestwicki JE Zuiderweg ER Allosteric drugs: The interaction of antitumor compound MKT-077 with human Hsp70 chaperones J Mol Biol 411 614 632 2011 10.1016/j.jmb.2011.06.003 21708173 PMC3146629 · DOI
  22. [22]Escobar-Henriques M Joaquim M Mitofusins: Disease gatekeepers and hubs in mitochondrial quality control by E3 Ligases Front Physiol 10 517 2019 10.3389/fphys.2019.00517 31156446 PMC6533591 · DOI
  23. [23]Head E Rofina J Zicker S Oxidative stress, aging, and central nervous system disease in the canine model of human brain aging Vet Clin North Am Small Anim Pract 38 167 178 2008 10.1016/j.cvsm.2007.10.002 18249248 PMC2390776 · DOI
  24. [24]Qadri R Goyal V Behari M Subramanian A Datta SK Mukhopadhyay AK Alteration of mitochondrial function in oxidative stress in parkinsonian neurodegeneration: A cross-sectional study Ann Indian Acad Neurol 24 506 512 2021 34728942 PMC8513980
  25. [25]Zhao J Dong L Huo T Cheng J Li X Huangfu X Sun S Wang H Li L O-GlcNAc Transferase (OGT) protects cerebral neurons from death during Ischemia/Reperfusion (I/R) injury by modulating Drp1 in mice Neuromolecular Med Oct 27 2021 (Epub ahead of print) 10.1007/s12017-021-08688-6 34705256 · DOI
  26. [26]Starenki D Sosonkina N Hong SK Lloyd RV Park JI Mortalin (GRP75/HSPA9) promotes survival and proliferation of thyroid carcinoma cells Int J Mol Sci 20 2069 2019 10.3390/ijms20092069 31027376 PMC6540051 · DOI
  27. [27]Zhang G Han M Wang X Xiao A GRP75 involves in retinal ganglion cell apoptosis after rat optic nerve crush J Mol Neurosci 56 422 430 2015 10.1007/s12031-015-0493-x 25600835 · DOI
  28. [28]D'Eletto M Rossin F Occhigrossi L Farrace MG Faccenda D Desai R Marchi S Refolo G Falasca L Antonioli M Piacentini, transglutaminase type 2 regulates ER-mitochondria contact sites by interacting with GRP75 Cell Rep 25 3573 3581 e3574 2018 10.1016/j.celrep.2018.11.094 30590033 · DOI
  29. [29]Brookes PS Yoon Y Robotham JL Anders MW Sheu SS Calcium, ATP, and ROS: A mitochondrial love-hate triangle Am J Physiol Cell Physiol 287 C817 C833 2004 10.1152/ajpcell.00139.2004 15355853 · DOI · Paper page
  30. [30]Verma M Wills Z Chu CT Excitatory dendritic mitochondrial calcium toxicity: Implications for Parkinson's and other neurodegenerative diseases Front Neurosci 12 523 2018 10.3389/fnins.2018.00523 30116173 PMC6083050 · DOI
  31. [31]Shan Y Cortopassi G Mitochondrial Hspa9/Mortalin regulates erythroid differentiation via iron-sulfur cluster assembly Mitochondrion 26 94 103 2016 10.1016/j.mito.2015.12.005 26702583 · DOI
  32. [32]Chen TH Kambal A Krysiak K Walshauser MA Raju G Tibbitts JF Walter MJ Knockdown of Hspa9, a del(5q31.2) gene, results in a decrease in hematopoietic progenitors in mice Blood 117 1530 1539 2011 10.1182/blood-2010-06-293167 21123823 PMC3056590 · DOI
  33. [33]Li X Srinivasan SR Connarn J Ahmad A Young ZT Kabza AM Zuiderweg ER Sun D Gestwicki JE Analogs of the allosteric heat shock protein 70 (Hsp70) inhibitor, MKT-077, as anti-cancer agents ACS Med Chem Lett 4 1042 1047 2013 10.1021/ml400204n 24312699 PMC3845967 · DOI
  34. [34]Miyata Y Li X Lee HF Jinwal UK Srinivasan SR Seguin SP Young ZT Brodsky JL Dickey CA Sun D Gestwicki JE Synthesis and initial evaluation of YM-08, a blood-brain barrier permeable derivative of the heat shock protein 70 (Hsp70) inhibitor MKT-077, which reduces tau levels ACS Chem Neurosci 4 930 939 2013 10.1021/cn300210g 23472668 PMC3689201 · DOI
  35. [35]Mylonis I Kourti M Samiotaki M Panayotou G Simos G Mortalin-mediated and ERK-controlled targeting of HIF-1α to mitochondria confers resistance to apoptosis under hypoxia J Cell Sci 130 466 479 2017 27909249

Cited by

Sorted by citations

Authors
Wen, B., Xu, K., Huang, R., Jiang, T., Wang, J., Chen, J., Chen, J., & He, B.
Affiliations
  • Huazhong University of Science and Technology (CN)
  • Department of Cardiovascular Medicine, Lichuan People's Hospital, Lichuan, Hubei 445400, P.R. China
Corresponding author
He, Benhong
ORCID
Venue
Molecular Medicine Reports
Publisher
Spandidos Publications
Published
2022-03-15
Volume
25
Issue
5
ISSN
  • 1791-2997 (ISSN-L)
  • 1791-3004
DOI
10.3892/mmr.2022.12681
PMC
PMC8941507
OpenAlex
W4220893636
Cited by
35
References
0
Citations by year
2026: 11 · 2025: 9 · 2024: 9 · 2023: 3 · 2022: 3
FWCI
1.96
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Molecular Medicine Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China (81873725)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
Keywords
ischemic stroke, GRP75, mitochondrial dysfunction, mitochondrial calcium overload, neuronal injury, mitochondrial fragmentation, middle cerebral artery occlusion, oxygen-glucose deprivation, hypoxia, neuroprotection
MeSH terms
Ischemic Stroke, Brain Ischemia, Humans, Membrane Proteins, Mitochondria, Neurons, HSP70 Heat-Shock Proteins, Stroke

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