PMID- 9298675
OWN - NLM
STAT- MEDLINE
DCOM- 19971022
LR  - 20190718
IS  - 0021-9150 (Print)
IS  - 0021-9150 (Linking)
VI  - 133
IP  - 2
DP  - 1997 Sep
TI  - The toxicity to macrophages of oxidized low-density lipoprotein is mediated 
      through lysosomal damage.
PG  - 153-61
AB  - Oxidized low-density lipoprotein (ox-LDL) has been shown to degrade poorly within 
      the secondary lysosomes of macrophages but its possible effect on lysosomal 
      integrity has received less attention. The effect of ultraviolet-C oxidized LDL 
      (UVox-LDL) on cellular viability, and lysosomal membrane stability, was examined 
      on cultured murine J-774 cells and human monocyte-derived macrophages (HMDMs). 
      The acridine orange (AO) relocalization test was applied to study the lysosomal 
      integrity of living cells. UVox-LDL dramatically reduced J-774 cell proliferation 
      at a concentration of 25 microg/ml. Incubation with 5 microM copper alone, 
      normally used to induce LDL oxidation, was also toxic. In contrast to the effects 
      of ox-LDL, in concentrations up to 75 microg/ml, native LDL (nLDL) rather 
      stimulated J-774 cell replication. Incubation with UVox-LDL (25-75 microg/ml) 
      also altered cellular AO uptake, depending on time and dose: its lysosomal 
      accumulation decreased and its cytosolic accumulation increased. This shift 
      indicates damaged lysosomal membranes with decreased intralysosomal, and 
      increased cytosolic, H+ concentration. Many J-774 cells exposed to UVox-LDL 
      initially transformed into foam cells and then assumed an apoptotic-type 
      morphology with TUNEL-positive nuclei. We conclude that ox-LDL is cytotoxic to 
      macrophages due to oxidative damage of lysosomal membranes, with ensuing 
      destabilization and leakage to the cytosol of lysosomal contents, such as 
      hydrolytic enzymes, causing degeneration of apoptotic type.
FAU - Yuan, X M
AU  - Yuan XM
AD  - Department of Internal Medicine, Faculty of Health Sciences, Linkoping 
      University, Sweden. yuan.ximing@ime.liu.se
FAU - Li, W
AU  - Li W
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  - Ireland
TA  - Atherosclerosis
JT  - Atherosclerosis
JID - 0242543
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (oxidized low density lipoprotein)
RN  - 789U1901C5 (Copper)
SB  - IM
MH  - Animals
MH  - Cell Division/drug effects/physiology
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Copper/toxicity
MH  - DNA Fragmentation/drug effects/physiology
MH  - Humans
MH  - Intracellular Membranes/drug effects/physiology
MH  - Lipoproteins, LDL/radiation effects/*toxicity
MH  - Lysosomes/*drug effects/*physiology/ultrastructure
MH  - Macrophages/cytology/*drug effects
MH  - Mice
MH  - Oxidation-Reduction/radiation effects
MH  - Ultraviolet Rays
EDAT- 1997/09/23 00:00
MHDA- 1997/09/23 00:01
CRDT- 1997/09/23 00:00
PHST- 1997/09/23 00:00 [pubmed]
PHST- 1997/09/23 00:01 [medline]
PHST- 1997/09/23 00:00 [entrez]
AID - S0021-9150(97)00094-4 [pii]
AID - 10.1016/s0021-9150(97)00094-4 [doi]
PST - ppublish
SO  - Atherosclerosis. 1997 Sep;133(2):153-61. doi: 10.1016/s0021-9150(97)00094-4.