PMID- 20943958
OWN - NLM
STAT- MEDLINE
DCOM- 20110204
LR  - 20231104
IS  - 1522-1563 (Electronic)
IS  - 0363-6143 (Print)
IS  - 0363-6143 (Linking)
VI  - 300
IP  - 1
DP  - 2011 Jan
TI  - Cystathionine beta-synthase and cystathionine gamma-lyase double gene transfer 
      ameliorate homocysteine-mediated mesangial inflammation through hydrogen sulfide 
      generation.
PG  - C155-63
LID - 10.1152/ajpcell.00143.2010 [doi]
AB  - Elevated level of homocysteine (Hcy) induces chronic inflammation in vascular 
      bed, including glomerulus, and promotes glomerulosclerosis. In this study we 
      investigated in vitro mechanism of Hcy-mediated monocyte chemoattractant 
      protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2) induction and 
      determined the regulatory role of hydrogen sulfide (H(2)S) to ameliorate 
      inflammation. Mouse glomerular mesangial cells (MCs) were incubated with Hcy (75 
      muM) and supplemented with vehicle or with H(2)S (30 muM, in the form of NaHS). 
      Inflammatory molecules MCP-1 and MIP-2 were measured by ELISA. Cellular 
      capability to generate H(2)S was measured by colorimetric chemical method. To 
      enhance endogenous production of H(2)S and better clearance of Hcy, cystathionine 
      beta-synthase (CBS) and cystathionine gamma-lyase (CSE) genes were delivered to the 
      cells. Oxidative NAD(P)H p47(phox) was measured by Western blot analysis and 
      immunostaining. Phosphorylation of extracellular signal-regulated kinase 1/2 
      (ERK1/2) and c-Jun NH(2)-terminal kinase (JNK1/2) were measured by Western blot 
      analysis. Our results demonstrated that Hcy upregulated inflammatory molecules 
      MCP-1 and MIP-2, whereas endogenous production of H(2)S was attenuated. H(2)S 
      treatment as well as CBS and CSE doubly cDNA overexpression markedly reduced 
      Hcy-induced upregulation of MCP-1 and MIP-2. Hcy-induced upregulation of 
      oxidative p47(phox) was attenuated by H(2)S supplementation and CBS/CSE 
      overexpression as well. In addition to that we also detected Hcy-induced MCP-1 
      and MIP-2 induction was through phosphorylation of ERK1/2 and JNK1/2. Either H(2)S 
      supplementation or CBS and CSE doubly cDNA overexpression attenuated Hcy-induced 
      phosphorylation of these two signaling molecules and diminished MCP-1 and MIP-2 
      expressions. Similar results were obtained by inhibition of ERK1/2 and JNK1/2 
      using pharmacological and small interferring RNA (siRNA) blockers. We conclude 
      that H(2)S plays a regulatory role in Hcy-induced mesangial inflammation and that 
      ERK1/2 and JNK1/2 are two signaling pathways involved this process.
FAU - Sen, Utpal
AU  - Sen U
AD  - Department of Physiology & Biophysics, University of Louisville, KY 40202, USA. 
      u0sen001@louisville.edu
FAU - Givvimani, Srikanth
AU  - Givvimani S
FAU - Abe, Oluwasegun A
AU  - Abe OA
FAU - Lederer, Eleanor D
AU  - Lederer ED
FAU - Tyagi, Suresh C
AU  - Tyagi SC
LA  - eng
GR  - HL-71010/HL/NHLBI NIH HHS/United States
GR  - HL-88012/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
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20101013
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CXCL2)
RN  - 0 (Cxcl2 protein, mouse)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 4.2.1.22 (Cystathionine beta-Synthase)
RN  - EC 4.4.1.1 (Cystathionine gamma-Lyase)
RN  - YY9FVM7NSN (Hydrogen Sulfide)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics/metabolism
MH  - Chemokine CXCL2/genetics/metabolism
MH  - Cystathionine beta-Synthase/genetics/*metabolism
MH  - Cystathionine gamma-Lyase/genetics/*metabolism
MH  - Extracellular Signal-Regulated MAP Kinases/genetics/metabolism
MH  - Gene Expression Regulation/physiology
MH  - Homocysteine/*metabolism
MH  - Hydrogen Sulfide/*metabolism
MH  - Inflammation/metabolism/*pathology
MH  - JNK Mitogen-Activated Protein Kinases/genetics/metabolism
MH  - Mesangial Cells/*metabolism
MH  - Mice
MH  - Signal Transduction/physiology
PMC - PMC3023186
EDAT- 2010/10/15 06:00
MHDA- 2011/02/05 06:00
PMCR- 2012/01/01
CRDT- 2010/10/15 06:00
PHST- 2010/10/15 06:00 [entrez]
PHST- 2010/10/15 06:00 [pubmed]
PHST- 2011/02/05 06:00 [medline]
PHST- 2012/01/01 00:00 [pmc-release]
AID - ajpcell.00143.2010 [pii]
AID - C-00143-2010 [pii]
AID - 10.1152/ajpcell.00143.2010 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2011 Jan;300(1):C155-63. doi: 
      10.1152/ajpcell.00143.2010. Epub 2010 Oct 13.