PMID- 9484981
OWN - NLM
STAT- MEDLINE
DCOM- 19980319
LR  - 20190831
IS  - 1079-5642 (Print)
IS  - 1079-5642 (Linking)
VI  - 18
IP  - 2
DP  - 1998 Feb
TI  - Uptake of oxidized LDL by macrophages results in partial lysosomal enzyme 
      inactivation and relocation.
PG  - 177-84
AB  - The cytotoxicity of oxidized LDL (oxLDL) to several types of artery wall cells 
      might contribute to atherosclerosis by causing cell death, presumably by both 
      apoptosis and necrosis. After its uptake into macrophage lysosomes by 
      receptor-mediated endocytosis, oxLDL is poorly degraded, resulting in 
      ceroid-containing foam cells. We studied the influence ofoxLDL on lysosomal 
      enzyme activity and, in particular, on lysosomal membrane stability and the 
      modulation of these cellular characteristics by HDL and vitamin E (vit-E). 
      Unexposed cells and cells exposed to acetylated LDL (AcLDL) were used as 
      controls. The lysosomal marker enzymes cathepsin L and 
      N-acetyl-beta-glucosaminidase (NAbetaGase) were biochemically assayed in J-774 
      cells after fractionation. Lysosomal integrity in living cells was assayed by the 
      acridine orange (AO) relocation test. Cathepsin D was immunocytochemically 
      demonstrated in J-774 cells and human monocyte-derived macrophages. We found that 
      the total activities of NAbetaGase and cathepsin L were significantly decreased, 
      whereas their relative cytosolic activities were enhanced, after oxLDL exposure. 
      Labilization of the lysosomal membranes was further proven by decreased lysosomal 
      AO uptake and relocation to the cytosol of cathepsin D, as estimated by light and 
      electron microscopic immunocytochemistry. HDL and vit-E diminished the 
      cytotoxicity of oxLDL by decreasing the lysosomal damage. The results indicate 
      that endocytosed oxLDL not only partially inactivates lysosomal enzymes but also 
      destabilizes the acidic vacuolar compartment, causing relocation of lysosomal 
      enzymes to the cytosol. Exposure to AcLDL resulted in its uptake with enlargement 
      of the lysosomal apparatus, but the stability of the lysosomal membranes was not 
      changed.
FAU - Li, W
AU  - Li W
AD  - Department of Pathology II, Clinical Research Centre, Faculty of Health Sciences, 
      University of Linkoping, Sweden. weili@pat.liu.se
FAU - Yuan, X M
AU  - Yuan XM
FAU - Olsson, A G
AU  - Olsson AG
FAU - Brunk, U T
AU  - Brunk UT
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (Enzymes)
RN  - 0 (Lipoproteins, HDL)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (oxidized low density lipoprotein)
RN  - 1406-18-4 (Vitamin E)
RN  - F30N4O6XVV (Acridine Orange)
SB  - IM
MH  - Acridine Orange
MH  - Animals
MH  - Biological Transport/physiology
MH  - Cell Line
MH  - Electrophoresis, Agar Gel
MH  - Enzyme Activation/physiology
MH  - Enzymes/metabolism
MH  - Humans
MH  - Lipoproteins, HDL/pharmacology
MH  - Lipoproteins, LDL/antagonists & inhibitors/*pharmacokinetics/pharmacology
MH  - Lysosomes/drug effects/*enzymology
MH  - Macrophages/*metabolism
MH  - Mice
MH  - Tissue Distribution
MH  - Vitamin E/pharmacology
EDAT- 1998/03/04 00:00
MHDA- 1998/03/04 00:01
CRDT- 1998/03/04 00:00
PHST- 1998/03/04 00:00 [pubmed]
PHST- 1998/03/04 00:01 [medline]
PHST- 1998/03/04 00:00 [entrez]
AID - 10.1161/01.atv.18.2.177 [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 1998 Feb;18(2):177-84. doi: 
      10.1161/01.atv.18.2.177.