PMID- 20395677
OWN - NLM
STAT- MEDLINE
DCOM- 20101012
LR  - 20220223
IS  - 1421-9670 (Electronic)
IS  - 0250-8095 (Print)
IS  - 0250-8095 (Linking)
VI  - 31
IP  - 5
DP  - 2010
TI  - Hydrogen sulfide regulates homocysteine-mediated glomerulosclerosis.
PG  - 442-55
LID - 10.1159/000296717 [doi]
AB  - BACKGROUND/AIMS: In this study we tested the hypothesis that H(2)S regulates 
      collagen deposition, matrix metalloproteinases (MMP) and inflammatory molecules 
      during hyperhomocysteinemia (HHcy) resulting in attenuation of glomerulosclerosis 
      and improved renal function. MATERIALS AND METHODS: A genetic model of HHcy, 
      cystathionine beta-synthase heterozygous (CBS+/-) and wild-type (WT) 2-kidney 
      (2K) mice were used in this study and supplemented with or without NaHS (30 
      micromol/l, H(2)S donor) in drinking water for 8 weeks. To expedite the renal 
      damage associated with HHcy, uninephrectomized (1K) mice of similar groups were 
      also used. RESULTS: Results demonstrated that NAD(P)H oxidase (p47(phox)subunit) 
      and blood pressure were upregulated in WT 1K, CBS+/- 2K and CBS+/- 1K mice with 
      downregulation of H(2)S production and reduced glomerular filtration rate. These 
      changes were normalized with H(2)S supplementation. Both pro- and active MMP-2 
      and -9 and collagen protein expressions and glomerular depositions were also 
      upregulated in WT 1K, CBS+/- 2K and CBS+/- 1K mice. Increased expressions of 
      inflammatory molecules, intercellular cell adhesion molecule-1 and vascular cell 
      adhesion molecule-1, as well as increased macrophage infiltration, were detected 
      in WT 1K, CBS+/- 2K and CBS+/- 1K mice. These changes were ameliorated with H(2)S 
      supplementation. CONCLUSION: Together, these results suggest that increased 
      oxidative stress and decreased H(2)S in HHcy causes matrix remodeling and 
      inflammation resulting in glomerulosclerosis and reduced renal function.
CI  - 2010 S. Karger AG, Basel.
FAU - Sen, Utpal
AU  - Sen U
AD  - Department of Physiology and Biophysics, University of Louisville School of 
      Medicine, Louisville, KY 40202, USA. u0sen001 @ louisville.edu
FAU - Munjal, Charu
AU  - Munjal C
FAU - Qipshidze, Natia
AU  - Qipshidze N
FAU - Abe, Oluwasegun
AU  - Abe O
FAU - Gargoum, Riyad
AU  - Gargoum R
FAU - Tyagi, Suresh C
AU  - Tyagi SC
LA  - eng
GR  - R01 HL074185/HL/NHLBI 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  - NS-51568/NS/NINDS 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
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100416
PL  - Switzerland
TA  - Am J Nephrol
JT  - American journal of nephrology
JID - 8109361
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 9007-34-5 (Collagen)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - EC 4.2.1.22 (Cystathionine beta-Synthase)
RN  - YY9FVM7NSN (Hydrogen Sulfide)
SB  - IM
MH  - Animals
MH  - Collagen/chemistry
MH  - Cystathionine beta-Synthase/metabolism
MH  - Down-Regulation
MH  - Homocysteine/*metabolism
MH  - Hydrogen Sulfide/*metabolism
MH  - Hyperhomocysteinemia/metabolism
MH  - Inflammation
MH  - Kidney/pathology
MH  - Kidney Diseases/*etiology/*metabolism
MH  - Male
MH  - Matrix Metalloproteinase 2/metabolism
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
PMC - PMC2883848
EDAT- 2010/04/17 06:00
MHDA- 2010/10/13 06:00
PMCR- 2011/05/01
CRDT- 2010/04/17 06:00
PHST- 2010/01/11 00:00 [received]
PHST- 2010/03/08 00:00 [accepted]
PHST- 2010/04/17 06:00 [entrez]
PHST- 2010/04/17 06:00 [pubmed]
PHST- 2010/10/13 06:00 [medline]
PHST- 2011/05/01 00:00 [pmc-release]
AID - 000296717 [pii]
AID - ajn0031-0442 [pii]
AID - 10.1159/000296717 [doi]
PST - ppublish
SO  - Am J Nephrol. 2010;31(5):442-55. doi: 10.1159/000296717. Epub 2010 Apr 16.