Recombinant truncated and microsomal heme oxygenase-1 and -2: differential sensitivity to inhibitors.
Recombinant truncated forms of heme oxygenase-1 and -2 (HO-1 and HO-2) were compared with their crude microsomal counterparts from brain and spleen tissue of adult male rats with respect to their inhibition by azole-based, nonporphyrin HO inhibitors. The drugs tested were an imidazole-alcohol, an imidazole-dioxolane, and a triazole-ketone. Both the recombinant and crude forms of HO-2 were similarly inhibited by the 3 drugs. The crude microsomal spleen form of HO-1 was more susceptible to inhibition than was the truncated recombinant form. This difference is attributed to the extra amino acids in the full-length enzyme. These observations may be relevant in the design of drugs as inhibitors of HO and other membrane proteins.
Vukomanovic
Dragic
D
Department of Pharmacology and Toxicology, Queen's University, Kingston, ON K7L 3N6, Canada.
McLaughlin
Brian
B
Rahman
Mona N
MN
Vlahakis
Jason Z
JZ
Roman
Gheorghe
G
Dercho
Ryan A
RA
Kinobe
Robert T
RT
Hum
Maaike
M
Brien
James F
JF
Jia
Zongchao
Z
Szarek
Walter A
WA
Nakatsu
Kanji
K
D000818:Animals; D001921:Brain / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors* / Q000737:chemistry; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008861:Microsomes / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D013154:Spleen / Q000201:enzymology; D014230:Triazoles / Q000737:chemistry / Q000494:pharmacology*
C552699:2-(2-(4-chlorophenyl)ethyl)-2-((1H-imidazol-1-yl)methyl)-1,3-dioxolane; C552698:4-(4-chlorophenyl)-1-(1H-imidazol-1-yl)butan-2-ol; C552700:4-phenyl-1-(1H-1,2,4-triazol-1-yl)-2-butanone; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011994:Recombinant Proteins; D014230:Triazoles; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C105245:heme oxygenase-2