PMID- 26254912
OWN - NLM
STAT- MEDLINE
DCOM- 20160824
LR  - 20181113
IS  - 1559-1166 (Electronic)
IS  - 0895-8696 (Linking)
VI  - 57
IP  - 4
DP  - 2015 Dec
TI  - Probucol Protects Against Asymmetric Dimethylarginine-Induced Apoptosis in the 
      Cultured Human Brain Microvascular Endothelial Cells.
PG  - 546-53
LID - 10.1007/s12031-015-0635-1 [doi]
AB  - Asymmetric dimethylarginine (ADMA) is emerging as a key contributor to 
      endothelial dysfunction. The drug probucol was reported to have an anti-lipid 
      peroxidation effect and improve endothelial dilation function. But little is 
      known about the protective effect of probucol on ADMA-induced human brain 
      microvascular endothelial cell (HBMEC) injury and its underlying mechanisms. 
      Therefore, in this study, we investigated the effect of probucol on ADMA-induced 
      HBMEC injury and its potential mechanisms. Results showed that probucol protected 
      against ADMA-induced HBMEC injury in a dose-dependent manner; probucol 
      pretreatment also significantly reduced the level of reactive oxygen species 
      (ROS) and malondialdehyde (MDA), downregulated the expression of pro-apoptotic 
      gene Bax and caspase-3 activity, as well as increased the brain-derived 
      neurotrophic factor (BDNF) release and promoted anti-apoptotic gene Bcl-2 and 
      eNOS expression in the cultured HBMECs. Furthermore, we found that ADMA 
      significantly increased the phosphorylation of c-Jun NH2-terminal kinase (JNK) 
      and p38, while probucol pretreatment effectively inhibited ADMA-induced JNK and 
      p38 phosphorylation in HBMECs. In conclusion, our present results demonstrated 
      that probucol protected against ADMA-induced HBMEC injury and suppressed 
      oxidative stress through the JNK/p38 MAPK pathway, which was the potential 
      underlying mechanism of HBMEC injury in ischemic cerebrovascular disease.
FAU - Ma, Jiwei
AU  - Ma J
AD  - Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical 
      University, No.88 Jiangkang Road, Xinxiang, Weihui, 453100, China.
FAU - Zhao, Shupeng
AU  - Zhao S
AD  - Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical 
      University, No.88 Jiangkang Road, Xinxiang, Weihui, 453100, China.
FAU - Gao, Guojun
AU  - Gao G
AD  - Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical 
      University, No.88 Jiangkang Road, Xinxiang, Weihui, 453100, China.
FAU - Chang, Haigang
AU  - Chang H
AD  - Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical 
      University, No.88 Jiangkang Road, Xinxiang, Weihui, 453100, China.
FAU - Ma, Pengju
AU  - Ma P
AD  - Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical 
      University, No.88 Jiangkang Road, Xinxiang, Weihui, 453100, China.
FAU - Jin, Baozhe
AU  - Jin B
AD  - Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical 
      University, No.88 Jiangkang Road, Xinxiang, Weihui, 453100, China. 
      baozhe_jin@163.com.
LA  - eng
PT  - Journal Article
DEP - 20150809
PL  - United States
TA  - J Mol Neurosci
JT  - Journal of molecular neuroscience : MN
JID - 9002991
RN  - 0 (Antioxidants)
RN  - 0 (dimethylarginine)
RN  - 94ZLA3W45F (Arginine)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 4)
RN  - P3CTH044XJ (Probucol)
SB  - IM
MH  - Antioxidants/*pharmacology
MH  - *Apoptosis
MH  - Arginine/analogs & derivatives/toxicity
MH  - Brain/blood supply
MH  - Cells, Cultured
MH  - Endothelial Cells/*drug effects/metabolism
MH  - Endothelium, Vascular/cytology
MH  - Humans
MH  - MAP Kinase Kinase 4/metabolism
MH  - Microvessels/cytology
MH  - Oxidative Stress
MH  - Probucol/*pharmacology
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
OTO - NOTNLM
OT  - Asymmetric dimethylarginine
OT  - Cell injury
OT  - Human brain microvascular endothelial cells
OT  - Probucol
OT  - Reactive oxygen species
EDAT- 2015/08/10 06:00
MHDA- 2016/08/25 06:00
CRDT- 2015/08/10 06:00
PHST- 2015/06/26 00:00 [received]
PHST- 2015/07/28 00:00 [accepted]
PHST- 2015/08/10 06:00 [entrez]
PHST- 2015/08/10 06:00 [pubmed]
PHST- 2016/08/25 06:00 [medline]
AID - 10.1007/s12031-015-0635-1 [pii]
AID - 10.1007/s12031-015-0635-1 [doi]
PST - ppublish
SO  - J Mol Neurosci. 2015 Dec;57(4):546-53. doi: 10.1007/s12031-015-0635-1. Epub 2015 
      Aug 9.