PMID- 15659799
OWN - NLM
STAT- MEDLINE
DCOM- 20050616
LR  - 20061115
IS  - 0077-8923 (Print)
IS  - 0077-8923 (Linking)
VI  - 1030
DP  - 2004 Dec
TI  - Enhanced expression of natural resistance-associated macrophage protein 1 in 
      atherosclerotic lesions may be associated with oxidized lipid-induced apoptosis.
PG  - 202-7
AB  - The natural resistance-associated macrophage proteins (Nramps) can modulate 
      inflammatory reactions. Nramps are not only responsible for intracellular 
      divalent metal transport but also determine the macrophage functions in 
      inflammatory processes. In the present study we tested whether Nramp1 is involved 
      in macrophage apoptosis induced by oxidized lipids in atherogenesis. Arterial 
      segments of Watanabe heritable hyperlipidemic rabbits were used for an 
      examination of Nramp1 mRNA by in situ RT-PCR and macrophage immunohistochemistry. 
      Annexin V/PI staining and terminal dUTP nick-end labeling (TUNEL) techniques were 
      used for apoptosis detection. We found that, in macrophage-rich areas (positive 
      to RMA-11) of the rabbit atherosclerotic aorta, there were lesion-dependent 
      increases in Nramp1 mRNA, which are mainly apoptotic foamy macrophages that are 
      positive to TUNEL staining. U937 cells were treated with 7beta-hydroxycholesterol 
      (7beta-OH) in the presence or absence of the redox-active iron chelator 
      desferrioxamine (DFO) or 1,10-phenanthroline. The cellular iron chelators 
      considerably reduced, whereas iron compounds enhanced, 7beta-OH-induced apoptosis 
      and necrosis. DFO also decreased mRNA levels of Nramp1, whereas both iron 
      compounds and 7beta-OH dramatically enhanced the expression of Nramp1 mRNA, 
      particularly among 7beta-OH-induced apoptotic cells. We conclude that the 
      enhanced expression of Nramp1 in macrophage regions of atherosclerotic lesions 
      may be associated with ferrous iron-enhanced, oxidized lipid-induced apoptosis. 
      This finding reveals a novel function of Nramp1 in atherogenesis.
FAU - Li, Wei
AU  - Li W
AD  - Division of Pathology II, Faculty of Health Sciences, Linkoping University, 
      Linkoping, Sweden.
FAU - Hellsten, Anna
AU  - Hellsten A
FAU - Nyhalah, Jerome Dinga
AU  - Nyhalah JD
FAU - Yuan, Xi-Ming
AU  - Yuan XM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Ann N Y Acad Sci
JT  - Annals of the New York Academy of Sciences
JID - 7506858
RN  - 0 (Cation Transport Proteins)
RN  - 0 (DNA Primers)
RN  - 0 (Hydroxycholesterols)
RN  - 0 (RNA, Messenger)
RN  - 0 (natural resistance-associated macrophage protein 1)
RN  - 566-26-7 (cholest-5-en-3 beta,7 alpha-diol)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Arteriosclerosis/*genetics/metabolism/pathology
MH  - Base Sequence
MH  - Cation Transport Proteins/*genetics/metabolism
MH  - DNA Primers
MH  - Humans
MH  - Hydroxycholesterols/*pharmacology
MH  - In Situ Nick-End Labeling
MH  - Oxidation-Reduction
MH  - RNA, Messenger/genetics
MH  - Rabbits
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 2005/01/22 09:00
MHDA- 2005/06/17 09:00
CRDT- 2005/01/22 09:00
PHST- 2005/01/22 09:00 [pubmed]
PHST- 2005/06/17 09:00 [medline]
PHST- 2005/01/22 09:00 [entrez]
AID - 1030/1/202 [pii]
AID - 10.1196/annals.1329.026 [doi]
PST - ppublish
SO  - Ann N Y Acad Sci. 2004 Dec;1030:202-7. doi: 10.1196/annals.1329.026.