PMID- 16309591
OWN - NLM
STAT- MEDLINE
DCOM- 20070111
LR  - 20131121
IS  - 1165-158X (Electronic)
IS  - 0145-5680 (Linking)
VI  - 51
IP  - 4
DP  - 2005 Sep 30
TI  - Carbon monoxide reduces the expression and activity of matrix metalloproteinases 
      1 and 2 in alveolar epithelial cells.
PG  - 403-8
AB  - Matrix metalloproteinases (MMPs), particularly MMP-1 and MMP-2, are involved in 
      the pathophysiology of emphysema. MMPs contain zinc in the catalytic site and its 
      expression is regulated transcriptionally via mitogen activated protein kinases 
      (MAPKs). Carbon monoxide (CO), one of the end products of heme oxygenase 
      activity, has anti-inflammatory properties, which are mediated, at least in part, 
      by activation of p38 MAPK. Furthermore, CO has the unique ability to bind to 
      metal centers in proteins and can affect their specific activity. Therefore, we 
      hypothesized that CO could inhibit MMPs expression and/or activity. Here we show 
      that a recently identified carbon monoxide-releasing molecule, [Ru(CO)3Cl2]2 (or 
      CORM-2) inhibits MMP-1 and MMP-2 mRNA expression in the human lung epithelial 
      cell line A549. The MMPs mRNA expression was unaffected by the p38 MAPK inhibitor 
      SB203580, but in the case of MMP-1 was reversed by the antioxidant 
      N-acetylcysteine. In addition, CORM-2 inhibited both MMP-1 and MMP-2 activities. 
      Interestingly, no effect was observed with (Ru(DMSO)4Cl2), a negative control 
      that does not contain CO groups. To the best of our knowledge this is the first 
      evidence on the effect of CO on MMPs expression and activity. This effect could 
      have important implications in the pathophysiology of emphysema and other 
      diseases involving proteases/antiproteases imbalance.
FAU - Desmard, M
AU  - Desmard M
AD  - Institut National de la Sante et la Recherche Medicale (INSERM) Unite 700, and 
      Institut Federatif de Recherche 02, Faculte de Medecine Xavier Bichat, 75018 
      Paris, France.
FAU - Amara, N
AU  - Amara N
FAU - Lanone, S
AU  - Lanone S
FAU - Motterlini, R
AU  - Motterlini R
FAU - Boczkowski, J
AU  - Boczkowski J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050930
PL  - France
TA  - Cell Mol Biol (Noisy-le-grand)
JT  - Cellular and molecular biology (Noisy-le-Grand, France)
JID - 9216789
RN  - 0 (Interleukin-1beta)
RN  - 0 (Organometallic Compounds)
RN  - 0 (RNA, Messenger)
RN  - 0 (tricarbonyldichlororuthenium (II) dimer)
RN  - 7U1EE4V452 (Carbon Monoxide)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - EC 3.4.24.7 (Matrix Metalloproteinase 1)
SB  - IM
MH  - Carbon Monoxide/*pharmacology
MH  - Cell Line, Tumor
MH  - Epithelial Cells/*drug effects/*enzymology
MH  - Gene Expression Regulation, Enzymologic/*drug effects
MH  - Humans
MH  - Interleukin-1beta/pharmacology
MH  - Matrix Metalloproteinase 1/genetics/*metabolism
MH  - Matrix Metalloproteinase 2/genetics/*metabolism
MH  - Organometallic Compounds/pharmacology
MH  - Pulmonary Alveoli/*cytology
MH  - RNA, Messenger/genetics
EDAT- 2005/11/29 09:00
MHDA- 2007/01/12 09:00
CRDT- 2005/11/29 09:00
PHST- 2005/04/14 00:00 [received]
PHST- 2005/05/12 00:00 [accepted]
PHST- 2005/11/29 09:00 [pubmed]
PHST- 2007/01/12 09:00 [medline]
PHST- 2005/11/29 09:00 [entrez]
AID - 403 [pii]
PST - epublish
SO  - Cell Mol Biol (Noisy-le-grand). 2005 Sep 30;51(4):403-8.