PMID- 22595990
OWN - NLM
STAT- MEDLINE
DCOM- 20121011
LR  - 20211021
IS  - 1522-1547 (Electronic)
IS  - 0193-1857 (Print)
IS  - 0193-1857 (Linking)
VI  - 303
IP  - 3
DP  - 2012 Aug 1
TI  - Hyperhomocysteinemia decreases intestinal motility leading to constipation.
PG  - G281-90
LID - 10.1152/ajpgi.00423.2011 [doi]
AB  - Elevated levels of plasma homocysteine (Hcy) called hyperhomocysteinemia (HHcy) 
      have been implicated in inflammation and remodeling in intestinal vasculature, 
      and HHcy is also known to aggravate the pathogenesis of inflammatory bowel 
      disease (IBD). Interestingly, colon is the pivotal site that regulates Hcy levels 
      in the plasma. We hypothesize that HHcy decreases intestinal motility through 
      matrix metalloproteinase-9 (MMP-9)-induced intestinal remodeling leading to 
      constipation. To verify this hypothesis, we used C57BL/6J or wild-type (WT), 
      cystathionine beta-synthase (CBS(+/-)), MMP-9(-/-), and MMP-9(-/-) + Hcy mice. 
      Intestinal motility was assessed by barium meal studies and daily feces output. 
      Plasma Hcy levels were measured by HPLC. Expression of ICAM-1, inducible nitric 
      oxide synthase, MMP-9, and tissue inhibitors of MMPs was studied by Western blot 
      and immunohistochemistry. Reactive oxygen species (ROS) including super oxide 
      were measured by the Invitrogen molecular probe method. Tissue nitric oxide 
      levels were assessed by a commercially available kit. Plasma Hcy levels in the 
      treated MMP-9 group mice were comparable to CBS(+/-) mice. Barium meal studies 
      suggest that intestinal motility is significantly decreased in CBS(+/-) mice 
      compared with other groups. Fecal output-to-body weight ratio was significantly 
      reduced in CBS(+/-) mice compared with other groups. There was significant 
      upregulation of MMP-9, iNOS, and ICAM-1 expression in the colon from CBS(+/-) 
      mice compared with WT mice. Levels of ROS, superoxide, and inducible nitric oxide 
      were elevated in the CBS(+/-) mice compared with other groups. Results suggest 
      that HHcy decreases intestinal motility due to MMP-9-induced intestinal 
      remodeling leading to constipation.
FAU - Givvimani, S
AU  - Givvimani S
AD  - Department of Physiology and Biophysics, University of Louisville School of 
      Medicine, Louisville, Kentucky 40202, USA. s0givv01@louisville.edu
FAU - Munjal, C
AU  - Munjal C
FAU - Narayanan, N
AU  - Narayanan N
FAU - Aqil, F
AU  - Aqil F
FAU - Tyagi, G
AU  - Tyagi G
FAU - Metreveli, N
AU  - Metreveli N
FAU - Tyagi, S C
AU  - Tyagi SC
LA  - eng
GR  - HL-71010/HL/NHLBI NIH HHS/United States
GR  - NS-51568/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120517
PL  - United States
TA  - Am J Physiol Gastrointest Liver Physiol
JT  - American journal of physiology. Gastrointestinal and liver physiology
JID - 100901227
RN  - 0 (Timp1 protein, mouse)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, mouse)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - EC 4.2.1.22 (Cystathionine beta-Synthase)
SB  - IM
MH  - Animals
MH  - Colon/*physiology
MH  - Constipation/*etiology
MH  - Cystathionine beta-Synthase/genetics
MH  - Feces
MH  - Gastrointestinal Motility/*drug effects
MH  - Hyperhomocysteinemia/complications/*physiopathology
MH  - Intercellular Adhesion Molecule-1/biosynthesis
MH  - Male
MH  - Matrix Metalloproteinase 9/biosynthesis/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nitric Oxide Synthase Type II/biosynthesis
MH  - Tissue Inhibitor of Metalloproteinase-1/biosynthesis
PMC - PMC3423105
EDAT- 2012/05/19 06:00
MHDA- 2012/10/12 06:00
PMCR- 2013/08/01
CRDT- 2012/05/19 06:00
PHST- 2012/05/19 06:00 [entrez]
PHST- 2012/05/19 06:00 [pubmed]
PHST- 2012/10/12 06:00 [medline]
PHST- 2013/08/01 00:00 [pmc-release]
AID - ajpgi.00423.2011 [pii]
AID - GI-00423-2011 [pii]
AID - 10.1152/ajpgi.00423.2011 [doi]
PST - ppublish
SO  - Am J Physiol Gastrointest Liver Physiol. 2012 Aug 1;303(3):G281-90. doi: 
      10.1152/ajpgi.00423.2011. Epub 2012 May 17.