TY - JOUR
T1 - Temperature-dependent quinone cytotoxicity in platelets involves arylation
AU - Kang, Young Ah
AU - Bae, Ok Nam
AU - Lee, Moo Yeol
AU - Chung, Seung Min
AU - Lee, Joo Young
AU - Chung, Jin Ho
PY - 2002/9/27
Y1 - 2002/9/27
N2 - Menadione (MEN), a representative quinone compound, produces cytotoxicity in many cells by arylation with protein thiols and oxidative stress due to redox cycling. Previously it was demonstrated that protein arylation appears to be a primary mechanism for MEN-induced toxicity in platelets. To test the hypothesis that temperature conditions may be important in MEN-induced cytotoxicity in noncancer cells, platelets were incubated with menadione at 25, 37, or 42°C. As temperature was increased, MEN significantly enhanced lactate dehydrogenase (LDH) leakage. MEN-induced depletion of protein thiol levels also increased as temperature was elevated. To investigate the mechanism of temperature-dependent MEN cytotoxicity, MEN-induced platelet toxicity was compared to two other quinone substances. Benzoquinone (BQ), which acts via arylation, produced cytotoxic effects similar to those of MEN. Dimethoxy- 1,4-naphthoquinone (DMNQ), which exerts toxicity via oxidative radical generation, failed to produce cytotoxicity at all three temperatures. While MEN and DMNQ enhanced O2 consumption in a temperature-dependent manner, BQ did not affect this parameter. MEN, which possesses an electrophilic 3-position, was found to react with thiols to form a thioether linkage, a direct indicator of arylation. In the case of MEN uptake kinetics, the amount of cellular uptake was not different at various temperatures, but concentration of MEN in extracellular medium decreased temperature dependently. This might be due to increased arylation capacity binding to cellular proteins as temperature rises. These data suggest that MEN-induced platelet cytotoxicity involves arylation that is temperature related.
AB - Menadione (MEN), a representative quinone compound, produces cytotoxicity in many cells by arylation with protein thiols and oxidative stress due to redox cycling. Previously it was demonstrated that protein arylation appears to be a primary mechanism for MEN-induced toxicity in platelets. To test the hypothesis that temperature conditions may be important in MEN-induced cytotoxicity in noncancer cells, platelets were incubated with menadione at 25, 37, or 42°C. As temperature was increased, MEN significantly enhanced lactate dehydrogenase (LDH) leakage. MEN-induced depletion of protein thiol levels also increased as temperature was elevated. To investigate the mechanism of temperature-dependent MEN cytotoxicity, MEN-induced platelet toxicity was compared to two other quinone substances. Benzoquinone (BQ), which acts via arylation, produced cytotoxic effects similar to those of MEN. Dimethoxy- 1,4-naphthoquinone (DMNQ), which exerts toxicity via oxidative radical generation, failed to produce cytotoxicity at all three temperatures. While MEN and DMNQ enhanced O2 consumption in a temperature-dependent manner, BQ did not affect this parameter. MEN, which possesses an electrophilic 3-position, was found to react with thiols to form a thioether linkage, a direct indicator of arylation. In the case of MEN uptake kinetics, the amount of cellular uptake was not different at various temperatures, but concentration of MEN in extracellular medium decreased temperature dependently. This might be due to increased arylation capacity binding to cellular proteins as temperature rises. These data suggest that MEN-induced platelet cytotoxicity involves arylation that is temperature related.
UR - http://www.scopus.com/inward/record.url?scp=0037183789&partnerID=8YFLogxK
U2 - 10.1080/00984100290071595
DO - 10.1080/00984100290071595
M3 - Article
C2 - 12227957
AN - SCOPUS:0037183789
SN - 1528-7394
VL - 65
SP - 1367
EP - 1378
JO - Journal of Toxicology and Environmental Health - Part A: Current Issues
JF - Journal of Toxicology and Environmental Health - Part A: Current Issues
IS - 18
ER -