Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The inducibility of aryl hydrocarbon hydroxylase (AHH) by benzo[a]-pyrene (BaP) has been studied in synchronously grown cultures of mouse liver cells. These cells (NMuLi cl 8) have low basal levels of AHH which can be induced greater than 100-fold by BaP. Cells were synchronized in G1(G0) by serum starvation and in S by release from serum starvation in combination with excess thymidine. When released from G1(G0) by replating at lower cell density in fresh medium with 20% serum, cells began entering S with a lag of 12 h. Addition of BaP (1 microgram/ml) 8 h before serum stimulation, at the time of stimulation or 7.5 h after stimulation all gave similar induction kinetics: the AHH activity peaked as the cells began entering S regardless of when the BaP was added. Cells blocked in various parts of S by excess thymidine were inducible for AHH activity as efficiently as cells moving through S and into G2. These results indicate that the inducibility of AHH is greater when cells are actively proliferating and may be a contributing factor to why growing cells are more sensitive to mutagenesis and transformation than quiescent cells.
 ...
PMID:Aryl hydrocarbon hydroxylase induction in mouse liver cells--relationship to position in the cell cycle. 50 89

The response of intestinal monooxygenases to dietary polycyclic aromatic hydrocarbon (PAH) exposure was evaluated in spot (Leiostomus xanthurus), a marine teleost fish. Ethoxyresorufin O-deethylase (EROD) and aryl hydrocarbon hydroxylase (AHH) activities were highest in the pyloric caeca and in the proximal half of the intestine. Intestinal microsomes from fish given control diets had very low levels of EROD and AHH activities relative to those in liver. After exposure to a diet containing 10 mg of 3-methylcholanthrene/kg of food, the levels of intestinal EROD and AHH activities increased 36-fold and 17-fold, respectively, such that intestinal monooxygenase activity exceeded that of the liver, which was not induced by this treatment. A significant increase in intestinal monooxygenase activity occurred in fish receiving dietary benzo[a]pyrene (BP) at concentrations as low as 10 micrograms of BP/kg food. A 5-fold increase in intestinal AHH and EROD activities was observed within 3 hr after administration of dietary BP. A plateau in gut monooxygenase activity occurred after approximately 3 days of PAH exposure; these activities decreased to control levels within 3 days after replacing the PAH diet with the control diet. Starvation resulted in disappearance of detectable monooxygenase activity. Monoclonal antibody (MAB 1-12-3) against the major PAH-inducible cytochrome P-450 (P-450E) in the liver of the marine teleost (Stenotomus chrysops) [Park et al. Arch. Biochem. Biophys. 249, 399 (1986)] recognized a single protein band in intestinal microsomes, with Mr near 54,000, which we conclude is the spot counterpart to cytochrome P-450E.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Induction of monooxygenase activity in the intestine of spot (Leiostomus xanthurus), a marine teleost, by dietary polycyclic aromatic hydrocarbons. 290 86

Two major forms of hepatic microsomal cytochrome P-450 were purified from starved and acetone-treated rats. On the basis of amino acid sequence analysis, they were identified as P-450j and P-450b. Ethanol or acetone treatment of rats caused a 9-fold increase in the amount of P-450j in liver microsomes accompanied by similar increases in the rate of NADPH-dependent metabolism of carbon tetrachloride, acetone, and benzene. Immunological experiments indicated that P-450j constitutes the major catalyst of the microsomal metabolism of the latter agents and contributes by about 50% to microsomal P-450-dependent ethanol oxidation under the conditions used. The P-450j-dependent catalytic activities had a high rate of turnover. In contrast, this was not the case for the immunodetectable P-450j, indicating the occurrence of inactive forms of this protein in microsomes. Starvation or ethanol or acetone treatment caused 10-30-fold increases in the amount of both mRNA and apoprotein of P-450b,e compared to control. Run-on experiments and the concomitant increases of the P-450b,e gene products at the mRNA and protein levels indicated the appearance of mainly a transcriptional activation by acetone, ethanol, or starvation. Fasting exerted, in addition, a pronounced synergistic effect on acetone-dependent induction of P-450b,e mRNA (3-fold), apo-P-450b,e (4.3-fold), P-450j mRNA (2-fold), and apo-P-450j (2-fold). No increase of mRNA coding for P-450j, compared to control, was seen after acetone or ethanol treatment alone. The results indicate that effects of ethanol, acetone, and/or starvation on drug and xenobiotic metabolism are caused by the induction of P-450 forms belonging to at least two gene subfamilies.
 ...
PMID:Ethanol-, fasting-, and acetone-inducible cytochromes P-450 in rat liver: regulation and characteristics of enzymes belonging to the IIB and IIE gene subfamilies. 337 38

Coho salmon exposed to the water soluble fraction (WSF) of Cook Inlet crude oil for a maximum of 30 days showed a greater than three-fold increase in hepatic aryl hydrocarbon hydroxylase activity. The initial increase in enzyme activity appeared between 2 and 5 days of exposure and increased as a function of increased exposure time. Persistence of the induced enzyme activity was dependent on the length and the concentration of WSF exposure. Handling stress had no effect on the AHH activity, but starvation caused a decrease in the activity.
 ...
PMID:Hepatic aryl hydrocarbon hydroxylase activities in coho salmon (Oncorhynchus kisutch) exposed to petroleum hydrocarbons. 615 64

Induction of aryl hydrocarbon hydroxylase (AHH) by polycyclic aromatic hydrocarbons and other inducers such as 2,3,8-tetrachlorodibenzo-p-dioxin (TCDD) is known to occur following binding of the inducer to a soluble receptor protein similar to steroid hormone receptors. This receptor is usually called the TCDD receptor, since TCDD has the highest affinity of all known ligands for the receptor. In the present paper a receptor for TCDD in cytosol from rat intestinal mucosa has been studied, using isoelectric focusing in polyacrylamide gel. This receptor's biochemical properties were found to be similar to those of the TCDD-receptor in rat liver cytosol. The dissociation constant (Kd) of the 3H-TCDD-receptor complex in rat intestinal mucosa was 0.7-3.1 nM, and it was present at a concentration of 70-80 fmol/mg protein. Starvation did not significantly increase the receptor level. The affinities of some potential dietary ligands for the TCDD receptor in rat intestinal mucosa were also studied. Indole-3-carbinol had 1/2,600 of the affinity of TCDD for the receptor protein. Butylated hydroxyanisole (BHA), transstilbene oxide and quercetinpentamethylether competed even more weakly with 3H-TCDD for binding to the receptor. The biological significance of the occurrence of low-affinity ligands of dietary origin for the TCDD receptor is uncertain at the present time.
 ...
PMID:The TCDD receptor in rat intestinal mucosa and its possible dietary ligands. 629 Oct 4

The binding of reactive benzo[a]pyrene metabolites to deproteinized DNA in vitro can be drastically changed, both quantitatively and qualitatively, in vitro by changes in the substrate concentration or the substrate/P-450 ratio, and in the intact animal by starvation or substitution of a 'purified protein test diet' for the regular laboratory chow. Liver, lung, and bowel microsomes from C57BL/6N and DBA/2N mice were examined. These data demonstrate the importance of dietary contaminants or nutrition during benzo[a]pyrene tumorigenesis. The profile of DNA binding of benzo[a]pyrene metabolites is also shown to be an extremely sensitive test for detecting minute amounts of induced cytochrome P1-450 and its associated aryl hydrocarbon (benzo[a]pyrene) hydroxylase (EC 1.14.14.2) activity. A direct correlation is not necessarily observed, however, between 'aryl hydrocarbon hydroxylase activity' and the amount of benzo[a]pyrene metabolites bound covalently to DNA. 'Untreated' genetically responsive mice are shown to have greater 'control' levels of benzo[a]pyrene metabolism in their various tissues than genetically nonresponsive mice simply on the basis that responsive mice have a lower threshold for 'responsiveness' to exogenous inducers inhaled and/or ingested in their crude diet, i.e., responsive 'control' animals already have partially induced enzymes.
 ...
PMID:DNA binding of benzo[a]pyrene metabolites. Effects of substrate and microsomal protein concentration in vitro, dietary contaminants, and tissue differences. 738 94

Ethanol, acetone, diet and starvation, known modulators of the hepatic cytochrome P450 (CYP)-dependent microsomal monooxygenase system, were assessed for their effects on cytochrome P450 isozyme content and monooxygenase activities in the male rat kidney. In acute experiments, rats were either treated with acetone, fasted or given a combination of the two treatments. Acetone treatment alone induced CYP2E1-dependent p-nitrophenol hydroxylase activity in kidney microsomes by 8-fold. This was accompanied by a 6-fold increase in CYP2E1 apoprotein as determined by Western blot analysis. There was, however, no significant increase in steady-state levels of CYP2E1 mRNA as measured by Northern blot analysis. Starvation also induced CYP2E1 apoprotein in the kidney and, as has been reported previously in the liver, had a synergistic inductive effect with acetone. CYP2B and CYP3A apoproteins were also induced by acetone, starvation and starvation/acetone combinations in the kidney. Immunohistochemical analysis revealed localization of CYP2E1 and CYP2B principally in the cortex associated with tubular cells. This distribution was maintained upon starvation/acetone treatment. Two induction experiments were performed in which the ethanol was administered as part of a system of total enteral nutrition (TEN). A short-term study was conducted in which ethanol was administered for 8 days in two liquid diets of different composition, and a chronic experiment was performed in which ethanol was administered for 35 days. A diet-independent 6-fold increase in CYP2E1 apoprotein was observed in the short-term experiment. Expression of CYP3A and CYP2A cross-reactive apoproteins in kidney microsomes appeared to be affected by alterations in diet but, were unaffected by ethanol treatment. In the chronic 35-day ethanol exposure experiment, CYP2E1 apoprotein was also elevated 6-fold and this was found to be accompanied by a significant 3-fold increase in CYP2E1 mRNA. In the same study, no ethanol effects were apparent on expression of CYP2B and CYP3A apoproteins. Thus, acetone induced a variety of renal cytochrome P450 forms in addition to CYP2E1, while ethanol appeared to be a much more specific renal CYP2E1 inducer. Furthermore, as reported in the liver, acetone and ethanol appeared to induce CYP2E1 in the kidney by different mechanisms.
 ...
PMID:Expression and distribution of cytochrome P450 enzymes in male rat kidney: effects of ethanol, acetone and dietary conditions. 944 34