PMID- 2304980
OWN - NLM
STAT- MEDLINE
DCOM- 19900327
LR  - 20190818
IS  - 0031-8655 (Print)
IS  - 0031-8655 (Linking)
VI  - 51
IP  - 1
DP  - 1990 Jan
TI  - Photooxidative damage to lysosomes of cultured macrophages by acridine orange.
PG  - 67-76
AB  - Cultured cells accumulate acridine orange (AO), which is a weak basic dye and a 
      photosensitizer, in lysosomes and other acidic compartments. During exposure to 
      blue light, AO-loaded macrophages show decreasing red granular fluorescence and 
      increasing green diffuse fluorescence. This is hypothesized to represent 
      peroxidative damage to lysosomal membranes resulting in an impaired proton 
      gradient with deprotonation of the AO to its uncharged form and subsequent 
      leakage of the dye. Further damage to the lysosomal membranes will result in 
      release of lytic enzymes from the lysosomal compartment into the cytosol, leading 
      to degeneration and finally cell death. The survival of AO-loaded and 
      light-exposed macrophages is controllable by varying the exposure times to blue 
      light. Inhibition of lysosomal proteases by E-64 results in increased cell 
      survival after AO and blue light-mediated damage, indicating a role of 
      proteolytic enzymes in this type of damage. Morphological analysis shows 
      'rounding up' with formation of retraction fibrils and pronounced plasma membrane 
      blebbing. The formation of autophagic vacuoles is an early and pronounced event. 
      After protease inhibition, however, all these phenomena are inhibitable to a 
      considerable degree. We have thus directed photooxidative damage selectively to 
      lysosomal membranes and their contents. This technique will allow further 
      detailed studies of the role of lysosomes in degeneration-regeneration processes.
FAU - Zdolsek, J M
AU  - Zdolsek JM
AD  - Department of Pathology II, University of Linkoping, Sweden.
FAU - Olsson, G M
AU  - Olsson GM
FAU - Brunk, U T
AU  - Brunk UT
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Photochem Photobiol
JT  - Photochemistry and photobiology
JID - 0376425
RN  - 0 (Cysteine Proteinase Inhibitors)
RN  - F30N4O6XVV (Acridine Orange)
RN  - GMW67QNF9C (Leucine)
RN  - R76F7856MV (E 64)
SB  - IM
MH  - Acridine Orange/*pharmacology
MH  - Animals
MH  - Cell Survival/drug effects/radiation effects
MH  - Cells, Cultured
MH  - Cysteine Proteinase Inhibitors
MH  - Fluorescence
MH  - Leucine/analogs & derivatives/pharmacology
MH  - *Light
MH  - Lysosomes/drug effects/*enzymology/radiation effects
MH  - Macrophages/*ultrastructure
MH  - Mice
MH  - Microscopy, Electron
MH  - Microscopy, Electron, Scanning
MH  - Oxidation-Reduction
EDAT- 1990/01/01 00:00
MHDA- 1990/01/01 00:01
CRDT- 1990/01/01 00:00
PHST- 1990/01/01 00:00 [pubmed]
PHST- 1990/01/01 00:01 [medline]
PHST- 1990/01/01 00:00 [entrez]
AID - 10.1111/j.1751-1097.1990.tb01685.x [doi]
PST - ppublish
SO  - Photochem Photobiol. 1990 Jan;51(1):67-76. doi: 
      10.1111/j.1751-1097.1990.tb01685.x.