PMID- 19913585
OWN - NLM
STAT- MEDLINE
DCOM- 20100708
LR  - 20211020
IS  - 1872-9754 (Electronic)
IS  - 0197-0186 (Print)
IS  - 0197-0186 (Linking)
VI  - 56
IP  - 2
DP  - 2010 Jan
TI  - Hydrogen sulfide mitigates matrix metalloproteinase-9 activity and neurovascular 
      permeability in hyperhomocysteinemic mice.
PG  - 301-7
LID - 10.1016/j.neuint.2009.11.002 [doi]
AB  - An elevated level of homocysteine (Hcy), known as hyperhomocysteinemia (HHcy), 
      was associated with neurovascular diseases. At physiological levels, hydrogen 
      sulfide (H(2)S) protected the neurovascular system. Because Hcy was also a 
      precursor of hydrogen sulfide (H(2)S), we sought to test whether the H(2)S 
      protected the brain during HHcy. Cystathionine-beta-synthase heterozygous 
      (CBS+/-) and wild type (WT) mice were supplemented with or without NaHS (30 
      microM/L, H(2)S donor) in drinking water. Blood flow and cerebral microvascular 
      permeability in pial vessels were measured by intravital microscopy in WT, 
      WT+NaHS, CBS-/+ and (CBS-/+)+NaHS-treated mice. The brain tissues were analyzed 
      for matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase 
      (TIMP) by Western blot and RT-PCR. The mRNA levels of CBS and cystathionine gamma 
      lyase (CSE, enzyme responsible for conversion of Hcy to H(2)S) genes were 
      measured by RT-PCR. The results showed a significant increase in MMP-2, MMP-9, 
      TIMP-3 protein and mRNA in CBS (-/+) mice, while H(2)S treatment mitigated this 
      increase. Interstitial localization of MMPs was also apparent through 
      immunohistochemistry. A decrease in protein and mRNA expression of TIMP-4 was 
      observed in CBS (-/+) mice. Microscopy data revealed increase in permeability in 
      CBS (-/+) mice. These effects were ameliorated by H(2)S and suggested that 
      physiological levels of H(2)S supplementation may have therapeutic potential 
      against HHcy-induced microvascular permeability, in part, by normalizing the 
      MMP/TIMP ratio in the brain.
CI  - Copyright 2009 Elsevier Ltd. All rights reserved.
FAU - Tyagi, Neetu
AU  - Tyagi N
AD  - Department of Physiology and Biophysics, School of Medicine, University of 
      Louisville, Louisville, KY 40202, USA. n0tyag01@louisville.edu
FAU - Givvimani, Srikanth
AU  - Givvimani S
FAU - Qipshidze, Natia
AU  - Qipshidze N
FAU - Kundu, Soumi
AU  - Kundu S
FAU - Kapoor, Shray
AU  - Kapoor S
FAU - Vacek, Jonathan C
AU  - Vacek JC
FAU - Tyagi, Suresh C
AU  - Tyagi SC
LA  - eng
GR  - R01 NS051568-05/NS/NINDS NIH HHS/United States
GR  - R01 HL071010/HL/NHLBI NIH HHS/United States
GR  - R01 NS051568/NS/NINDS NIH HHS/United States
GR  - R01 HL088012/HL/NHLBI NIH HHS/United States
GR  - R01 HL088012-04/HL/NHLBI NIH HHS/United States
GR  - NS-51568/NS/NINDS NIH HHS/United States
GR  - R01 HL074185-07/HL/NHLBI NIH HHS/United States
GR  - HL-74185/HL/NHLBI NIH HHS/United States
GR  - HL-88012/HL/NHLBI NIH HHS/United States
GR  - HL-71010/HL/NHLBI NIH HHS/United States
GR  - R01 HL074185/HL/NHLBI NIH HHS/United States
GR  - R01 HL071010-08/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20091112
PL  - England
TA  - Neurochem Int
JT  - Neurochemistry international
JID - 8006959
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - YY9FVM7NSN (Hydrogen Sulfide)
SB  - IM
MH  - Animals
MH  - Capillary Permeability/*drug effects
MH  - Hydrogen Sulfide/*pharmacology
MH  - Hyperhomocysteinemia/enzymology/*physiopathology
MH  - Matrix Metalloproteinase 9/*metabolism
MH  - Mice
MH  - Reverse Transcriptase Polymerase Chain Reaction
PMC - PMC2921887
MID - NIHMS162822
EDAT- 2009/11/17 06:00
MHDA- 2010/07/09 06:00
PMCR- 2011/01/01
CRDT- 2009/11/17 06:00
PHST- 2009/11/01 00:00 [received]
PHST- 2009/11/03 00:00 [accepted]
PHST- 2009/11/17 06:00 [entrez]
PHST- 2009/11/17 06:00 [pubmed]
PHST- 2010/07/09 06:00 [medline]
PHST- 2011/01/01 00:00 [pmc-release]
AID - S0197-0186(09)00305-2 [pii]
AID - 10.1016/j.neuint.2009.11.002 [doi]
PST - ppublish
SO  - Neurochem Int. 2010 Jan;56(2):301-7. doi: 10.1016/j.neuint.2009.11.002. Epub 2009 
      Nov 12.