Disease relevance of Cyp2c

• We hypothesized that the downregulation of Cyp2c by tumor necrosis factor (TNF) alpha contributes to hypertension and renal injury in salt-sensitive angiotensin hypertension [1].
• The present study was performed to investigate the role of vasopressin in long-term regulation of UT1 and UT2 in neurogenic diabetes insipidus (Brattleboro) rats treated with a 7-day continuous infusion of [Arg(8)]-vasopressin (AVP), [deamino-Cys(1), D-Arg(8)]-vasopressin (dDAVP) or vehicle [2].
• Impaired expression of microsomal cytochrome P450 2C11 in choline-deficient rat liver during the development of cirrhosis [3].
• Cytochrome P450 2C11: Escherichia coli expression, purification, functional characterization, and mechanism-based inactivation of the enzyme [4].

High impact information on Cyp2c

• Recently, three types of urea transporters have been cloned, UT1 and UT2 from rat and rabbit kidney and HUT11 from human bone marrow [5].
• Inhibitors of vesicular transport decreased flow cytometric recognition of both unalkylated and tienilic acid-alkylated cytochrome P450 2C11 on the plasma membrane of cultured hepatocytes [6].
• Cytochrome P450 2C11 was the main microsomal or plasma membrane protein that was alkylated by tienilic acid [6].
• Restoration of cytochrome P450 2C11 in vitamin A-deficient rat liver by exogenous androgen [7].
• Cyclophosphamide modulates rat hepatic cytochrome P450 2C11 and steroid 5 alpha-reductase activity and messenger RNA levels through the combined action of acrolein and phosphoramide mustard [8].

Biological context of Cyp2c

• Studies in Sprague-Dawley rats showed that restriction of water intake for 3 days results in upregulation of urea transporter (UT) mRNA in the inner stripe of outer medulla of the kidney (2.9-kb UT2) but not in the inner medulla (4.0-kb UT1) [2].
• The kinetics of the four major cytochrome P-450s (P-450 UT-2, UT-4, PB-4, and MC-5) for aminopyrine N-demethylation and hydroxylation activities were studied [9].
• Renal epithelia express at least two distinct urea transporter mRNAs, termed UT1 and UT2, that are derived from a single UT gene by alternative splicing [10].
• Regulation of cytochrome P450 2C11 (CYP2C11) gene expression by interleukin-1, sphingomyelin hydrolysis, and ceramides in rat hepatocytes [11].
• We have examined the role of sphingomyelin hydrolysis to ceramide in the suppression of CYP2C11, a major constitutive form of cytochrome P450, by interleukin-1 [11].

Anatomical context of Cyp2c

• Triazoles affected the expression of numerous CYP genes in rat liver and testis, including multiple Cyp2c and Cyp3a isoforms as well as other xenobiotic metabolizing enzyme (XME) and transporter genes [12].
• These activities of hepatic microsomes were reduced with the decrease in P450 UT-2 [13].
• The metabolism of lidocaine was studied using rat liver microsomes or a reconstituted lidocaine monooxygenase system with one of eight forms of cytochrome P-450 purified from liver microsomes from untreated- (P450 UT-2 and UT-5), phenobarbital- (P450 PB-1, PB-2, PB-4, and PB-5) or 3-methylcholanthrene- (P450 MC-1 and MC-5) treated rats [14].
• Antigenic targets in tienilic acid hepatitis. Both cytochrome P450 2C11 and 2C11-tienilic acid adducts are transported to the plasma membrane of rat hepatocytes and recognized by human sera [6].
• The UT2 cells grown in the absence of mevalonate containing the up-regulated peroxisomal HMG-CoA reductase are designated UT2*. A detailed characterization and analysis of this cell line is presented in this study [15].

Associations of Cyp2c with chemical compounds

• P450 UT-2 had high testosterone 2 alpha- and 16 alpha-hydroxylation activities [13].
• P450 UT-2 was active in demethylation of benzphetamine, P450 UT-4 was active in the metabolism of 7-ethoxycoumarin and p-nitroanisole [16].
• The NH2-terminal sequences of six forms of cytochrome P-450 (designated P450 UT-1, UT-2, UT-4, UT-5, UT-7 and UT-8) indicate that these cytochrome P-450 isozymes are of different molecular species [16].
• Our studies reveal the role of vasopressin in long-term regulation of UT1 and UT2 expression during water restriction [2].
• Anti-P-450 UT-2 IgG fraction obtained from rabbit serum dose-dependently suppressed formations of 16 alpha-OH-T, 2 alpha-OH-T, and androstenedione from testosterone with liver microsomes of adult male rats [17].

Regulatory relationships of Cyp2c

• In situ hybridization further demonstrated that the UT2 signal is upregulated and spread along the descending thin limbs of loops of Henle and that UT1 signal is downregulated in the inner medullary collecting ducts in vasopressin-treated rats, with a greater response for dDAVP compared with the AVP-treated group [2].

Other interactions of Cyp2c

• P450 UT-2 (P450h) and P450 UT-5 (P450g), typical male-specific forms, decreased with starvation [13].
• P450 UT-1 and P450 UT-2 were active in the 2 alpha- and 16 alpha-hydroxylation of testosterone, whereas P450 UT-4 was active in the 6 beta-, 7 alpha- and 15 alpha-hydroxylation of the same steroid [16].
• Fibronectin-mediated hepatocyte shape change reprograms cytochrome P450 2C11 gene expression via an integrin-signaled induction of ribonuclease activity [18].
• These results suggest a role for glucagon in the down-regulation of CYP2C11 in diabetic rats, and provide a possible explanation for the known sensitivity of this cytochrome P450 to suppression in various stress and disease models [19].
• These results indicate, for the first time, that neonatal BaP exposure results in gender-specific lasting effects on hepatic cytochrome P450 1A2, cytochrome P450 2C11, and glucocorticoid receptors in adult male rats, whereas these parameters are unchanged in adult female rats [20].

Analytical, diagnostic and therapeutic context of Cyp2c

• Immunocytochemistry studies revealed that the UT1 and UT2 proteins are also modified in the same pattern as the transcript changes [2].
• Northern analysis showed that water restriction alone had no effect on the level of UT2 mRNA in vehicle-treated Brattleboro rats but UT2 mRNA markedly increased and UT1 mRNA modestly decreased after treatment with dDAVP [2].
• In contrast, P-450 UT-A (a male specific form) decreased drastically from 295 pmol/mg in the control group to about 10% of this value in diabetic rats and to 50% in fasting rats [21].
• Immunofluorescence and immunoperoxidase staining confirmed the presence of cytochromes P-450 UT-A, PB-B and ISF-G on the membrane [22].
• In two experiments, hypophysectomy (Hx) resulted in decreased (P < .05) hepatic CYP2C11 apoprotein and mRNA levels [23].

References