![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 283, Issue 3, 1479-1485, 1997
Departments of
Biochemistry (Y.M., Y.T., M.I.) and
Surgery (S.T.)
and
Laboratory of Chemistry (S.I., Y.F.), Osaka City University Medical
School, Abeno-ku, Osaka 545, Japan; and
Department of Surgery (S.T.),
Osaka Kita Municipal Hospital, Konohana-ku, Osaka 554, Japan
Nitric oxide (NO) modulates various metabolisms through interaction
with thiol proteins and hemoproteins. Although NO interacts reversibly
with iron moieties of heme proteins, including cytochrome P450 (P450),
dynamic aspects of the formation, catalytic functions and fates of
NO-P450 adducts remain to be elucidated. When incubated with NOC7,
which spontaneously and stoichiometrically releases NO within 5 min,
microsomal P450 rapidly formed nitrosyl-heme adducts as determined by
the electron spin resonance method. The signal intensity for the
complex increased with time, peaking at 30 min and decreasing to below
detectable levels by 60 min of incubation. In contrast, the microsomal
levels of low-spin ferric forms of P450 (g = 2.26)
rapidly decreased during the initial 30 min but recovered
time-dependently thereafter. Analysis by differential spectra (reduced
form/CO-reduced form) revealed that on incubation with NOC7, the form
of microsomal P450 also changed in a biphasic manner. To elucidate the
mechanism for the decrease in the levels of P450, microsomal levels of
P450 isozymes (CYPs) were determined by Western blot analysis using
specific antibodies against CYP3A2 and CYP2C11, major isoforms found in
male rat liver. Kinetic analysis revealed that no appreciable
degradation of P450 proteins occurred during the incubation of
microsomes with NOC7. The effect of NO on the catalytic activity of the
enzymes was determined by using testosterone as substrate
because hydroxylation of steroid hormones is one of the
major functions of P450. When exposed to NO, the hydroxylation activity
in microsomes rapidly decreased during the initial 10 min and then
disappeared slowly. These results suggested that NO formed dissociable
complexes with P450 isozymes and the catalytic functions of these
isozymes were irreversibly inactivated after dissociation from their
heme moiety.
This article has been cited by other articles:
|
|
 |
|
  C. W. Jin, S. T. Du, Y. S. Zhang, X. Y. Lin, and C. X. Tang Differential regulatory role of nitric oxide in mediating nitrate reductase activity in roots of tomato (Solanum lycocarpum) Ann. Bot., July 1, 2009; 104(1): 9 - 17. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Masubuchi, K. Enoki, and T. Horie Down-Regulation of Hepatic Cytochrome P450 Enzymes in Rats with Trinitrobenzene Sulfonic Acid-Induced Colitis Drug Metab. Dispos., March 1, 2008; 36(3): 597 - 603. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-M. Lee, B.-Y. Kim, L. Li, and E. T. Morgan Nitric Oxide-dependent Proteasomal Degradation of Cytochrome P450 2B Proteins J. Biol. Chem., January 11, 2008; 283(2): 889 - 898. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Xu, R.H. Henning, E. Lipsic, A. van Buiten, W.H. van Gilst, and H. Buikema Acetylcholine stimulated dilatation and stretch induced myogenic constriction in mesenteric artery of rats with chronic heart failure Eur J Heart Fail, February 1, 2007; 9(2): 144 - 151. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Vuppugalla and R. Mehvar SELECTIVE EFFECTS OF NITRIC OXIDE ON THE DISPOSITION OF CHLORZOXAZONE AND DEXTROMETHORPHAN IN ISOLATED PERFUSED RAT LIVERS Drug Metab. Dispos., July 1, 2006; 34(7): 1160 - 1166. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. McNeish, S. L. Sandow, C. B. Neylon, M. X. Chen, K. A. Dora, and C. J. Garland Evidence for Involvement of Both IKCa and SKCa Channels in Hyperpolarizing Responses of the Rat Middle Cerebral Artery Stroke, May 1, 2006; 37(5): 1277 - 1282. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Kourylko, C. Fradette, M. Arcand, and P. du Souich MODULATION OF CYP1A2 AND CYP3A6 CATALYTIC ACTIVITIES BY SERUM FROM RABBITS WITH A TURPENTINE-INDUCED INFLAMMATORY REACTION AND INTERLEUKIN 6 Drug Metab. Dispos., January 1, 2006; 34(1): 27 - 35. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Huang, Y. Zhou, V. T. Raju, J. Du, H.-H. Chang, C.-Y. Wang, M. W. Brands, J. R. Falck, and M.-H. Wang Renal 20-HETE inhibition attenuates changes in renal hemodynamics induced by L-NAME treatment in pregnant rats Am J Physiol Renal Physiol, November 1, 2005; 289(5): F1116 - F1122. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Vuppugalla and R. Mehvar ENZYME-SELECTIVE EFFECTS OF NITRIC OXIDE ON AFFINITY AND MAXIMUM VELOCITY OF VARIOUS RAT CYTOCHROMES P450 Drug Metab. Dispos., June 1, 2005; 33(6): 829 - 836. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Vuppugalla and R. Mehvar SHORT-TERM INHIBITORY EFFECTS OF NITRIC OXIDE ON CYTOCHROME P450-MEDIATED DRUG METABOLISM: TIME DEPENDENCY AND REVERSIBILITY PROFILES IN ISOLATED PERFUSED RAT LIVERS Drug Metab. Dispos., December 1, 2004; 32(12): 1446 - 1454. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Vuppugalla and R. Mehvar Hepatic Disposition and Effects of Nitric Oxide Donors: Rapid and Concentration-Dependent Reduction in the Cytochrome P450-Mediated Drug Metabolism in Isolated Perfused Rat Livers J. Pharmacol. Exp. Ther., August 1, 2004; 310(2): 718 - 727. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Moore, M. M. Nakano, T. Wang, R. W. Ye, and J. D. Helmann Response of Bacillus subtilis to Nitric Oxide and the Nitrosating Agent Sodium Nitroprusside J. Bacteriol., July 15, 2004; 186(14): 4655 - 4664. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Minamiyama, S. Takemura, K. Yamasaki, S. Hai, K. Hirohashi, Y. Funae, and S. Okada Continuous Administration of Organic Nitrate Decreases Hepatic Cytochrome P450 J. Pharmacol. Exp. Ther., February 1, 2004; 308(2): 729 - 735. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-i. Komine, T. Kuroishi, Y. Komine, K. Watanabe, J. Kobayashi, T. Yamaguchi, S.-i. Kamata, and K. Kumagai Induction of Nitric Oxide Production Mediated by Tumor Necrosis Factor Alpha on Staphylococcal Enterotoxin C-Stimulated Bovine Mammary Gland Cells Clin. Vaccine Immunol., January 1, 2004; 11(1): 203 - 210. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. C Hercule, M.-H. Wang, and A. O Oyekan Contribution of cytochrome P450 4A isoforms to renal functional response to inhibition of nitric oxide production in the rat J. Physiol., September 15, 2003; 551(3): 971 - 979. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-H. Wang, J. Wang, H.-H. Chang, B. A. Zand, M. Jiang, A. Nasjletti, and M. Laniado-Schwartzman Regulation of renal CYP4A expression and 20-HETE synthesis by nitric oxide in pregnant rats Am J Physiol Renal Physiol, August 1, 2003; 285(2): F295 - F302. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. T. Morgan, V. Ullrich, A. Daiber, P. Schmidt, N. Takaya, H. Shoun, J. C. McGiff, A. Oyekan, C. J. Hanke, W. B. Campbell, et al. Cytochromes P450 and Flavin Monooxygenases---Targets and Sources of Nitric Oxide Drug Metab. Dispos., November 1, 2001; 29(11): 1366 - 1376. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Ferrari, N. Peng, J. R. Halpert, and E. T. Morgan Role of Nitric Oxide in Down-Regulation of CYP2B1 Protein, but Not RNA, in Primary Cultures of Rat Hepatocytes Mol. Pharmacol., July 1, 2001; 60(1): 209 - 216. [Abstract] [Full Text]
|
|
|
|
 |
|
 K. Kitaichi, L. Wang, K. Takagi, M. Iwase, E. Shibata, M. Nadai, K. Takagi, and T. Hasegawa Decreased Antipyrine Clearance following Endotoxin Administration: In Vivo Evidence of the Role of Nitric Oxide Antimicrob. Agents Chemother., November 1, 1999; 43(11): 2697 - 2701. [Abstract] [Full Text]
|
|
|
|
 |
|
 C. J. M. Kerkhof, E. N. T. P. Bakker, and P. Sipkema Role of cytochrome P-450 4A in oxygen sensing and NO production in rat cremaster resistance arteries Am J Physiol Heart Circ Physiol, October 1, 1999; 277(4): H1546 - H1552. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-S. Park, H.-M. Baek, W.-G. Chung, K.-H. Lee, S.-D. Ryu, and Y.-N. Cha Suppression of Flavin-Containing Monooxygenase by Overproduced Nitric Oxide in Rat Liver Mol. Pharmacol., September 1, 1999; 56(3): 507 - 514. [Abstract] [Full Text]
|
|
|
|
 |
|
 G. Cucchiaro, A. H. Tatum, M. C. Brown, E. M. Camporesi, J. W. Daucher, and T. S. Hakim Inducible nitric oxide synthase in the lung and exhaled nitric oxide after hyperoxia Am J Physiol Lung Cell Mol Physiol, September 1, 1999; 277(3): L636 - L644. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. B. Sewer and E. T. Morgan Down-Regulation of the Expression of Three Major Rat Liver Cytochrome P450S by Endotoxin In Vivo Occurs Independently of Nitric Oxide Production J. Pharmacol. Exp. Ther., October 1, 1998; 287(1): 352 - 358. [Abstract] [Full Text]
|
|
|
|
|
|
M. B. Sewer, T. B. Barclay, and E. T. Morgan Down-Regulation of Cytochrome P450 mRNAs and Proteins in Mice Lacking a Functional NOS2 Gene Mol. Pharmacol., August 1, 1998; 54(2): 273 - 279. [Abstract] [Full Text]
|
|
 |
 |
 |
|
 |
 |
 |
