The effect of sulindac on arylamine N-acetyltransferase activity in Pseudomonas aeruginosa.
Arylamine N-acetyltransferase (NAT) activity in Pseudomonas aeruginosa was inhibited by sulindac, a drug proposed for cancer prevention. By using high performance liquid chromatography, the NAT activity for acetylation of 2-aminofluorene (2-AF) was examined. The cytosolic NAT activity in P. aeruginosa ATCC 27853 was 5.32 +/- 0.36 nmol/min/mg of protein. Sulindac displayed a dose-dependent inhibition to cytosolic NAT activity in P. aeruginosa with an IC50 value of about 0.46 mM. The NAT activity measured from intact P. aeruginosa cells was 1.39 +/- 0.12 nmol/min/10(10) CFU and this activity was inhibited by sulindac in a similar dose-dependent fashion with an IC50 value of approximately 0.42 mM. Time-course experiments showed that NAT activity measured from intact P. aeruginosa cells was inhibited by sulindac for at least 3 h. Using standard steady-state kinetic analysis, it was demonstrated that sulindac was a possible noncompetitive inhibitor to NAT activity in P. aeruginosa. The results suggest that sulindac suppressed the NAT activity in P. aeruginosa.
Lo
H H
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Department of Medical Technology, Chungtai Junior College, Taichung, Taiwan, Republic of China.
Hsieh
S E
SE
Chung
J G
JG
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001191:Arylamine N-Acetyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002273:Carcinogens / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005449:Fluorenes / Q000378:metabolism; D006801:Humans; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000201:enzymology; D013467:Sulindac / Q000494:pharmacology*; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001426:Bacterial Proteins; D002273:Carcinogens; D005449:Fluorenes; D013467:Sulindac; C012177:2-aminofluorene; D001191:Arylamine N-Acetyltransferase