Oxygen-Glucose Deprivation Induces G2/M Cell Cycle Arrest in Brain Pericytes Associated with ERK Inactivation.
Growing evidence has revealed that brain pericytes are multifunctional and contribute to the pathogenesis of a number of neurological disorders. However, the role of pericytes in cerebral ischemia, and especially the pathophysiological alterations in pericytes, remains unclear. In the present study, our aim was to determine whether the proliferation of pericytes is affected by cerebral ischemia and, if so, to identify the underlying mechanism(s). Cultured brain pericytes subjected to oxygen-glucose deprivation (OGD) were used as our model of cerebral ischemia; the protein expression levels of cyclin D1, cyclin E, cdk4, and cyclin B1 were determined by Western blot analysis, and cell cycle analysis was assessed by flow cytometry. The OGD treatment reduced the brain pericyte proliferation by causing G2/M phase arrest and downregulating the protein levels of cyclin D1, cyclin E, cdk4, and cyclin B1. Further studies demonstrated a simultaneous decrease in the activity of extracellular regulated protein kinases (ERK), suggesting a critical role of the ERK signaling cascade in the inhibition of OGD-induced pericyte proliferation. We suggest that OGD inhibition of the proliferation of brain pericytes is associated with the inactivation of the ERK signaling pathway, which arrests them in the G2/M phase.
Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
Wenjie
W
Wei
Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
Zhiyuan
Z
Yu
Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
Minjie
M
Xie
Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
Wei
W
Wang
Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China. tjhfile@tjh.tjmu.edu.cn.
Xiang
X
Luo
D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D015687:Cell Hypoxia; D002478:Cells, Cultured; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D059565:G2 Phase Cell Cycle Checkpoints; D005947:Glucose / Q000172:deficiency*; D020935:MAP Kinase Signaling System; D008297:Male; D010100:Oxygen / Q000378:metabolism*; D020286:Pericytes / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D016213:Cyclins; D005947:Glucose; D010100:Oxygen
Cell cycle; ERK; Oxygen-glucose deprivation; Pericyte
J Cereb Blood Flow Metab. 2013 Mar;33(3):428-39
23250106
Nat Med. 2009 Nov;15(11):1298-306
19881493
J Neurosci Res. 1998 Sep 15;53(6):637-44
9753191
Prog Neurobiol. 2009 Sep;89(1):1-17
19619927
Circulation. 2004 Oct 12;110(15):2226-32
15466630
Cell Stem Cell. 2008 Sep 11;3(3):301-13
18786417
J Pathol. 2009 Jan;217(2):318-24
19023885
Nature. 2006 Oct 12;443(7112):700-4
17036005
J Biol Chem. 1996 Aug 23;271(34):20608-16
8702807
Acta Neuropathol. 2014 Sep;128(3):381-96
24848101
Dev Cell. 2011 Aug 16;21(2):193-215
21839917
Brain Pathol. 2014 Jul;24(4):371-86
24946075
Cancer Sci. 2006 Aug;97(8):697-702
16800820
Sci Rep. 2012;2:220
22355734
Neurochem Int. 2011 Aug;59(2):259-71
21672581
J Biol Chem. 2001 Jun 22;276(25):22404-9
11304535
Nat Med. 2009 Sep;15(9):1031-7
19718040
Brain Res. 2005 Mar 21;1038(2):208-15
15757636
Anticancer Res. 2009 Jan;29(1):449-53
19331185
J Clin Endocrinol Metab. 2009 Sep;94(9):3171-82
19509100
Science. 1989 Nov 3;246(4930):629-34
2683079
Nature. 2008 Dec 11;456(7223):809-13
18997771
Fluids Barriers CNS. 2015 Feb 17;12:4
25879623
J Cereb Blood Flow Metab. 2006 May;26(5):613-24
16421511
Am J Hematol. 2010 Aug;85(8):593-8
20540157
Microvasc Res. 2000 Jul;60(1):55-69
10873515
Nat Commun. 2013;4:2932
24336108
Nature. 2010 Nov 25;468(7323):562-6
20944625
J Biol Chem. 2002 Dec 6;277(49):47469-75
12359725
Proc Natl Acad Sci U S A. 2010 Dec 21;107(51):22290-5
21135230
Cell Mol Neurobiol. 2007 Sep;27(6):687-94
17823866
Nature. 2011 May 19;473(7347):298-307
21593862
BMC Cancer. 2007 Jan 12;7:8
17222343
Oncogene. 2007 May 14;26(22):3227-39
17496918
Cell Prolif. 2000 Oct;33(5):261-74
11063129
Arch Ophthalmol. 1968 Sep;80(3):332-7
4174771