PMID- 28975464
OWN - NLM
STAT- MEDLINE
DCOM- 20180816
LR  - 20191008
IS  - 1573-6903 (Electronic)
IS  - 0364-3190 (Print)
IS  - 0364-3190 (Linking)
VI  - 43
IP  - 2
DP  - 2018 Feb
TI  - Peroxynitrite-Induced Tyrosine Nitration Contributes to Matrix Metalloprotease-3 
      Activation: Relevance to Hyperglycemic Ischemic Brain Injury and Tissue 
      Plasminogen Activator.
PG  - 259-266
LID - 10.1007/s11064-017-2411-9 [doi]
AB  - Matrix metalloprotease-3 (MMP3) activation mediates the tissue plasminogen 
      activator (tPA)-induced hemorrhagic transformation after stroke. Hyperglycemia 
      (HG) further exacerbates this outcome. We have recently shown that HG increases 
      MMP3 activity in the brain after stroke. However, the combined HG-tPA effect on 
      MMP3 activation, and the mechanisms through which MMP3 is activated were not 
      previously reported. Accordingly, this study tested the hypothesis that tPA and 
      HG increases MMP3 activity in the brain after stroke through peroxynitrite 
      induced tyrosine nitration. Normoglycemic and mildly hyperglycemic male Wistar 
      rats were subjected to middle cerebral artery suture occlusion for 90 min or 
      thromboembolic occlusion, and up to 24 h reperfusion, with and without tPA. MMP3 
      activity and tyrosine nitration were evaluated in brain homogenates at 24 h. 
      Brain microvascular endothelial cells (BMVEC) were subjected to either 3 h 
      hypoxia or 6 h OGD under either normal or high glucose conditions with or without 
      tPA, with or without peroxynitrite scavenger, FeTPPs. MMP3 activity and MMP3 
      tyrosine nitration were assessed at 24 h. HG and tPA significantly increased 
      activity and tyrosine nitration of MMP3 in the brain. In BMVECs, tPA but not HG 
      increased MMP3 activity. Treating BMVEC with FeTPPs significantly reduced the 
      tPA-induced increase in MMP3 activity and nitration. Augmented oxidative and 
      nitrative stress may be potential mechanisms contributing to MMP3 activation in 
      hyperglycemic stroke, especially with tPA administration. Peroxynitrite may be 
      playing a critical role in mediating MMP3 activation through tyrosine nitration 
      in hyperglycemic stroke.
FAU - Hafez, Sherif
AU  - Hafez S
AD  - Charlie Norwood Veterans Administration Medical Center, Augusta, GA, 30912, USA.
AD  - Program in Clinical and Experimental Therapeutics, College of Pharmacy, 
      University of Georgia, Augusta, GA, 30912, USA.
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, Larkin University, 
      Miami, FL, 33169, USA.
FAU - Abdelsaid, Mohammed
AU  - Abdelsaid M
AD  - Department of Biomedical Sciences, School of Medicine, Mercer University, 
      Savannah, GA, 31404, USA.
FAU - Fagan, Susan C
AU  - Fagan SC
AD  - Charlie Norwood Veterans Administration Medical Center, Augusta, GA, 30912, USA.
AD  - Program in Clinical and Experimental Therapeutics, College of Pharmacy, 
      University of Georgia, Augusta, GA, 30912, USA.
AD  - Department of Neurology, Medical College of Georgia, Augusta University, Augusta, 
      GA, 30912, USA.
FAU - Ergul, Adviye
AU  - Ergul A
AD  - Charlie Norwood Veterans Administration Medical Center, Augusta, GA, 30912, USA. 
      aergul@augusta.edu.
AD  - Program in Clinical and Experimental Therapeutics, College of Pharmacy, 
      University of Georgia, Augusta, GA, 30912, USA. aergul@augusta.edu.
AD  - Department of Physiology, Medical College of Georgia, Augusta University, 
      Augusta, GA, 30912, USA. aergul@augusta.edu.
LA  - eng
GR  - R01 NS063965/NS/NINDS NIH HHS/United States
GR  - I01 BX000891/BX/BLRD VA/United States
GR  - R01 NS083559/NS/NINDS NIH HHS/United States
GR  - R01NS083559/National Institutes of Health/
GR  - I01 BX000347/BX/BLRD VA/United States
GR  - 13PRE17090026/American Heart Association/
PT  - Journal Article
DEP - 20171003
PL  - United States
TA  - Neurochem Res
JT  - Neurochemical research
JID - 7613461
RN  - 14691-52-2 (Peroxynitrous Acid)
RN  - 42HK56048U (Tyrosine)
RN  - EC 3.4.21.68 (Tissue Plasminogen Activator)
RN  - EC 3.4.24.17 (MMP3 protein, human)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Animals
MH  - Brain/drug effects
MH  - Brain Ischemia/drug therapy/*metabolism
MH  - Cerebral Hemorrhage/chemically induced
MH  - Disease Models, Animal
MH  - Male
MH  - Matrix Metalloproteinase 3/*metabolism
MH  - Peroxynitrous Acid/*pharmacology
MH  - Rats, Wistar
MH  - Reperfusion Injury/drug therapy
MH  - Tissue Plasminogen Activator/*metabolism
MH  - Tyrosine/metabolism
PMC - PMC5801117
MID - NIHMS910636
OTO - NOTNLM
OT  - Hemorrhagic transformation
OT  - Hyperglycemia
OT  - Matrix metalloprotease 3
OT  - Peroxynitrite
OT  - Tissue plasminogen activator
COIS- Conflict of Interest Sherif Hafez declares that he has no conflict of interest. 
      Mohammed Abdelsaid declares that he has no conflict of interest. Susan C. Fagan 
      declares that she has no conflict of interest. Adviye Ergul declares that she has 
      no conflict of interest.
EDAT- 2017/10/05 06:00
MHDA- 2018/08/17 06:00
PMCR- 2019/02/01
CRDT- 2017/10/05 06:00
PHST- 2017/03/27 00:00 [received]
PHST- 2017/09/26 00:00 [accepted]
PHST- 2017/09/20 00:00 [revised]
PHST- 2017/10/05 06:00 [pubmed]
PHST- 2018/08/17 06:00 [medline]
PHST- 2017/10/05 06:00 [entrez]
PHST- 2019/02/01 00:00 [pmc-release]
AID - 10.1007/s11064-017-2411-9 [pii]
AID - 10.1007/s11064-017-2411-9 [doi]
PST - ppublish
SO  - Neurochem Res. 2018 Feb;43(2):259-266. doi: 10.1007/s11064-017-2411-9. Epub 2017 
      Oct 3.