PMID- 16225842
OWN - NLM
STAT- MEDLINE
DCOM- 20051230
LR  - 20131121
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 337
IP  - 4
DP  - 2005 Dec 2
TI  - Upregulation of aldose reductase by homocysteine in type II alveolar epithelial 
      cells.
PG  - 1084-91
AB  - Homocysteine (Hcy) has recently been recognized as an integral component of 
      several disorders. However, the association between hyperhomocysteinemia (HHcy) 
      and pulmonary disease is not well understood. The combination of two-dimensional 
      electrophoresis and tandem mass spectrometry detected and identified proteins 
      that are differentially expressed in human type II alveolar epithelial cells 
      (A549 cells) treated by Hcy. We found that aldose reductase (AR) showed more 
      abundant expression in the cells. Further, Hcy (100-500microM) could induce a 
      time- and dose-dependent upregulation of AR protein levels. Immunohistochemical 
      staining of cross-sections from HHcy mice lungs also revealed increased 
      expression of AR protein. Intracellular levels of reactive oxygen species (ROS) 
      were remarkably elevated in A549 cells treated with Hcy. Pretreatment of A549 
      cells with catalase and SOD significantly suppressed the Hcy-induced AR 
      expression, which suggests the involvement of ROS in this process. The major 
      signaling pathway mediating the upregulation of AR was demonstrated to be the 
      Ras/Raf/ERK1/2 pathway. In addition, Hcy might reduce surfactant protein B (SP-B) 
      expression in the cells, which could be significantly attenuated by Alrestatin, 
      an AR inhibitor, indicating a damaging role of Hcy-induced AR elevation in the 
      lung. These results show a novel and unanticipated link between HHcy and AR 
      upregulation that may be a risk factor in pulmonary disease of patients with 
      HHcy.
FAU - Jiang, He
AU  - Jiang H
AD  - Department of Physiology and Pathophysiology, Key Laboratory of Molecular 
      Cardiovascular Science, Ministry of Education, School of Basic Medical Science, 
      Peking University, Beijing 100083, People's Republic of China.
FAU - Wang, Xiao Fei
AU  - Wang XF
FAU - Fang, Liang
AU  - Fang L
FAU - Tang, Chaoshu
AU  - Tang C
FAU - Zhu, Yi
AU  - Zhu Y
FAU - Wang, Xian
AU  - Wang X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20051005
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Proteome)
RN  - 0 (Reactive Oxygen Species)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - EC 1.1.1.21 (Aldehyde Reductase)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Aldehyde Reductase/*metabolism
MH  - Alveolar Process/*cytology
MH  - Cell Line, Tumor
MH  - Enzyme Induction/*drug effects
MH  - Epithelial Cells/*drug effects/*enzymology
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Homocysteine/*pharmacology
MH  - Humans
MH  - Proteome/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction/drug effects
EDAT- 2005/10/18 09:00
MHDA- 2005/12/31 09:00
CRDT- 2005/10/18 09:00
PHST- 2005/09/05 00:00 [received]
PHST- 2005/09/15 00:00 [accepted]
PHST- 2005/10/18 09:00 [pubmed]
PHST- 2005/12/31 09:00 [medline]
PHST- 2005/10/18 09:00 [entrez]
AID - S0006-291X(05)02120-0 [pii]
AID - 10.1016/j.bbrc.2005.09.160 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2005 Dec 2;337(4):1084-91. doi: 
      10.1016/j.bbrc.2005.09.160. Epub 2005 Oct 5.