摘要:

Three models have been proposed for substrate-induced spin-state transition in cytochrome P450. These are referred to as two-three- and four-state models. In this communication the three models are reviewed with respect to their experimental basis and their ability to accommodate the results reported on the effects of substrates on spin-state and reduction of various P450′s. In addition, a new perspective is presented.

ISSN:0743-5800    

DOI:10.1080/07435809309026680

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Ovariectomized mice were either sham operated or sialoadenectomized and injected daily for 18 days with saline, estradiol + progesterone, cholera toxin or estradiol + progesterone + cholera toxin. Mammary development score and DNA were increased by estradiol + progesterone, but not by cholera toxin alone. In combination with estradiol + progesterone, cholera toxin increased mammary development score and mammary DNA. Sialoadenectomy reduced the ability of estradiol, progesterone and cholera toxin to induce mammary development. In other experiments, mice were primed with estradiol + progesterone for 10 days, and mammary tissue removed for in vitro culture with various combinations of insulin, aldosterone, cholera toxin and epidermal growth factor. In combination with insulin and aldosterone, cholera toxin increased mammary development in vitro. Sialoadenectomy reduced the ability of cholera toxin to induce mammary development in vitro. The effect of sialoadenectomy on mammary development was alleviated by adding epidermal growth factor to culture medium. Biochemical studies indicated that sialoadenectomy reduced the ability of estrogen and progesterone to induce cyclic AMP dependent protein kinase levels in mammary tissue, and also the ability of cholera toxin to induce accumulation of cyclic AMP in tissues. These effects of sialoadenectomy were reversed by addition of EGF to culture media.

ISSN:0743-5800    

DOI:10.1080/07435809309026681

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Effects of genistein on insulin release were studied using MIN6 cells, a glucose-sensitive insulinoma cell line. At the non-stimulatory concentrations of glucose, genistein did not affect insulin release, however, at the stimulatory concentrations of glucose, genistein significantly increased insulin release in a dose-dependent manner up to 20μg/ml. The content of cAMP in MIN6 cells was also elevated significantly by genistein and the dose-response relationship between the genistein and cAMP accumulation was consistent with the relationship between the genistein and insulin release. These effects were inhibited by calcium antagonists or by the omission of extracellular calcium. Isobutylmethylxanthine(IBMX;0.1mM) increased both cAMP accumulation and insulin release in MIN6 cells and there were no additive effects by the addition of genistein. The accumulation of cAMP might have, at least in part, resulted from phosphodiesterase inhibition by genistein. These results suggest that genistein augments glucose-induced insulin release by the contribution of cAMP accumulation and calcium modulation which depends on extracellular calcium.

ISSN:0743-5800    

DOI:10.1080/07435809309026682

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

The effect of altered thyroid status and food-deprivation on palmitic acid oxidation in isolated rat liver mitochondria was studied in the absence and presence of digitonin. Mitochondria prepared from triiodothyronine-treated (hyperthyroid) and food-deprived rats metabolized palmitic acid at the same rate as the untreated controls (euthyroid). Mitochondria prepared from thyroidectomized (hypothyroid) rats metabolized palmitic acid at a rate lower than was that seen with mitochondria from euthyroid controls in either the fed or fasted state. Fasting had no effect on palmitic acid oxidation by mitochondria prepared from euthyroid rats but diminished the rates seen in both hyper-and hypothyroid states. Digitonin (0.04 mg/ mg mitochondrial protein) increased the sensitivity of the rate of fatty acid oxidation to inhibition byα-bromopalmitic acid. The addition of digitonin to the incubation mixture resulted in two-fold increases in the rate of palmitic acid oxidation in all states. This study shows that the limitations imposed by hypothyroidism on fatty acid oxidation in intact liver are preserved in isolated mitochondria.

ISSN:0743-5800    

DOI:10.1080/07435809309026683

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Galanin is able to enhance growth hormone (GH)-releasing hormone stimulated GH secretion in normal man. In acromegaly circulating GH levels are elevated and the GH response to GHRH may be exaggerated. Galanin has been recently shown to decrease circulating GH levels in acromegaly. Dopaminergic drugs were the only previously known agents able to cause a paradoxical GH fall in acromegaly. Aim of our study was to investigate the effects of a potent central dopaminergic receptor blocker, metoclopramide (MCP), on the galanin-induced paradoxical GH secretion in acromegalic subjects. Two male and three female patients with active acromegaly (age range 44–66 years, body mass index range 24.6–28 Kg/m2) were studied after 45 min iv infusion of porcine galanin (0.5 mg in 100 ml of saline) from 0 to 45 min combined with a 60 min iv infusion of a) saline (100 ml) or b) MCP (10 mg in 100 ml of saline) from -15 to 45 min. After galanin, GH values fell from baseline (27.5±10μg/L) to a mean nadir of 16.4±6.1μg/L; after galanin+MCP, circulating GH levels were also decreased (mean nadir 17.3±8.1μg/L) in all the patients with respect to baseline (23.6±9.7μg/L). No significant differences were found in absolute or percent of baseline GH levels after galanin±saline vs galanin+MCP. Our results suggest that the paradoxical GH fall after galanin in acromegalic patients is not mediated through dopaminergic receptor. It can be hypothesized that galanin may interact at the pituitary level with its own receptors expressed by GH-secreting adenomatous cells.

ISSN:0743-5800    

DOI:10.1080/07435809309026684

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

The recent availability of genetically altered rat lines differing in sensitivity to ethanol (EtOH) has allowed deeper investigation into the mechanisms of EtOH-induced cellular toxicity in several systems. Since the male central reproductive axis has been demonstrated to be exquisitely sensitive to EtOH, studies were undertaken to determine if the gonadotropin suppression reported earlier could be duplicated in one of these selected rat lines.Castrated high alcohol sensitivity (HAS), low alcohol sensitivity (LAS) and control alcohol sensitivity (CAS) rats were given EtOH or saline acutely. Castrated non-selectively bred Sprague Dawley rats were treated similarily and used as an additional control. At sacrifice, serum and pituitary luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels were obtained and the mRNA levels for both gonadotropins assessed.In the selectivity bred animal there was essentially no change in serum or pituitary LH or FSH levels between EtOH and saline treated animals. The mRNA levels for both LH and FSH similarly were unaffected by EtOH, in striking contrast to the non-selectively bred Sprague Dawley rats where serum LH, FSH andβ-LH mRNA levels are markedly suppressed after EtOH exposure.The selectively bred lines of rats genetically manipulated for high or low EtOH sensitivity, as well as their non-selected controls, appeared to have a hypothalamic-pituitary reproductive unit that is resistant to EtOH. This is in contrast to Sprague-Dawley rats, where suppression of this axis previously has been consistently demonstrated.

ISSN:0743-5800    

DOI:10.1080/07435809309026685

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor