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.
Department of Medical Technology, Chungtai Junior College, Taichung, Taiwan, Republic of China.
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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