The proportion of peripheral blood lymphocytes with cell surface b5 immunoglobulin (Ig) was compared with serum b5 Ig levels in allotype-suppressed and recovering b5 homozygous rabbits in order to establish the cellular defect in suppression and to determine the relation between lymphocyte membrane Ig and secreted Ig of the same allotype. In rabbits fully suppressed for b5, the absence of circu...

Methoxyflurane is an anesthetic whose metabolism by cytochrome P-450LM2 has been shown to be dependent upon a heat-stable microsomal protein (Canova-Davis, E., and Waskell, L. A. (1982) Biochem. Biophys. Res. Commun. 108, 1264-1270). Treatment of this protein with diethylpyrocarbonate, which modifies selected amino acids, caused a dose-dependent loss in its ability to effect the metabolism of m...

Human cytochrome b5 (Cyt b5) plays important roles in cytochrome P450 (CYP)-mediated drug metabolism. However, the expression level of Cyt b5 in normal human liver remains largely unknown. The effect of Cyt b5 on overall CYP activity in human liver microsomes (HLM) has rarely been reported and the relationship between Cyt b5 and the activity of polymorphic CYP has not been systematically invest...

The hemoprotein cytochrome b(5) (cyt b5) has been demonstrated to affect the kinetics of drug oxidation by the microsomal cytochromes P450 (P450s). However, the mechanisms through which cyt b5 exerts these effects are variable and P450 isoform-dependent. Whereas the effects of cyt b5 on the major drug-metabolizing enzymes CYP2D6, CYP2E1, and CYP3A4 are well studied, fewer studies conducted over...

Furamidine is an effective antimicrobial agent; however, oral potency of furamidine is poor. A prodrug of furamidine, 2,5-bis(4-amidinophenyl)furan-bis-O-methylamidoxime (DB289), has greatly improved oral potency. DB289 is transformed to furamidine via O-demethylation, and N-dehydroxylation reactions with four intermediate metabolites formed. The O-demethylation reactions have been shown to be ...

The synthetic curcumin analog B5 is a potent inhibitor of thioredoxin reductase (TrxR) that has potential anticancer effects. The molecular mechanism underlying B5 as an anticancer agent is not yet fully understood. In this study, we report that B5 induces apoptosis in two human cervical cancer cell lines, CaSki and SiHa, as evidenced by the downregulation of XIAP, activation of caspases and cl...

Cytochrome b5 (cyt b5) genes encode ubiquitous electron transport hemoproteins found in animals, plants, fungi, and purple bacteria. However, little is known about their evolutionary history in genomes so far. Here, we conducted an extensive genome-wide survey of cyt b5 genes in 20 representative model species and identified 310 of these genes. Both the absolute number and relative proportion o...

Experiments demonstrating that cytochrome (cyt) b5 inhibits the activity of cytochrome P450 2B4 (cyt P450 2B4) at higher concentrations suggested that cyt b5 was occupying the cyt P450 reductase-binding site on cyt P450 2B4 and preventing the reduction of ferric cyt P450 (Zhang, H., Im, S.-C., and Waskell, L. (2007) J. Biol. Chem. 282, 29766-29776). In this work experiments were undertaken with...

In the course of a screening program for inhibitors of epidermal growth factor (EGF)-induced phosphatidylinositol turnover in human epidermoid carcinoma cell line A431, we discovered two novel compounds of the piericidin family from the culture broth and mycelia of a Streptomyces strain MJ288-OF3. We named them piericidin B5 and B5 N-oxide. By NMR and mass spectrometric analyses, the molecular ...