Regulation of respiratory activity of brown adipose tissue mitochondria through changes in cytochromes.

Exposure of cold-acclimatized rats to heat (37 degrees C) for a short period decreased brown adipose tissue (BAT) mitochondrial substrate-dependent oxygen uptake and H2O2 generation. Both the concentration and substrate-dependent rate of cytochrome b reduction decreased as early as 3 h of heat exposure. These results identify cytochrome b as the locus of regulation of electron transport in BAT mitochondria under conditions of heat stress.

Developmental regulation of cytochrome P-450 (b+e) and glutathione transferase (Ya+Yc) gene expression in rat liver

The expression of cytochrome P-450 (b+e) and glutathione transferase (Ya+Yc) genes has been studied as a function of development in rat liver. The levels of cytochrome P-450 (b+e) mRNAs and their transcription rates are too low for detection in the 19-day old fetal liver before or after phenobarbitone treatment. However, glutathione transferase (Ya+Yc) mRNAs can be detected in the fetal liver as well as their induction after phenobarbitone treatment can be demonstrated. These mRNAs contents as well as their inducibility with phenobarbitone are lower in maternal liver than that of adult nonpregnant female rat liver. Steroid hormone administration to immature rats blocks substantially the phenobarbitone mediated induction of the two mRNA families as well as their transcription. It is suggested that steroid hormones constitute one of the factors responsible for the repression of the cytochrome P-450 (b+e) and glutathione transferase (Ya+Yc) genes in fetal liver.

Role of oestradiol-17β in the regulation of synthesis and secretion of human chorionic gonadotrophin by first trimester human placenta

Inhibition of aromatase, a key enzyme in the biosynthesis of oestradiol-17 beta, by the addition of 1,4,6-androstatrien-3,17-dione resulted in a significant increase in the levels of immunoreactive human chorionic gonadotrophin (hCG) in the medium and tissue. This increase was partially reversed by the simultaneous addition of oestradiol-17 beta. These effects on the levels of immunoreactive hCG were also reflected by the increased levels of mRNA specific for the alpha and beta subunits of hCG following the addition of the aromatase inhibitor. However, addition of tamoxifen resulted in a drastic decrease in the levels of both the messages. Based on these results, it is suggested that the synthesis of hCG is negatively modulated by oestradiol-17 beta in the human placenta.

Specificity in the regulation of eukaryotic gene transcription

The regulation of eukaryotic gene transcription poses major challenges in terms of the innumerable protein factors required to ensure tissue or cell-type specificity. While this specificity is sought to be explained by the interaction of cis-acting DNA elements and thetrans-acting protein factor(s), considerable amount of degeneracy has been observed in this interaction. Immunoglobulin heavy chain gene expression in B cells and liver-specific gene expression are discussed as examples of this complexity in this article. Heterodimerization and post-translational modification of transcription factors and the organization of composite promoter elements are strategies by which diverse sets of genes can be regulated in a specific manner using a finite number of protein factors

Functions Of Cytochrome-C In Regulation Of Electron-Transfer And Protein Folding

Cytochrome c, a "mobile electron carrier" of the mitochondrial respiratory chain, also occurs in detectable amounts in the cytosol, and can receive electrons from cytochromes present in endoplasmic reticulum and plasma membranes as well as from superoxide and ascorbate. The pigment was found to dissociate from mitochondrial membranes in liver and kidney when rats were subjected to heat exposure and starvation, respectively. Treating cytochrome c with hydroxylamine gives a partially deaminated product with altered redox properties; decreased stimulation of respiration by deficient mitochondria, increased reduction by superoxide, and complete loss of reducibility by plasma membranes. Mitochondria isolated from brown adipose tissue of cold-exposed rats are found to be sub-saturated with cytochrome c. The ability of cytochrome c to reactivate reduced ribonuclease is now reinterpreted as a molecular chaperone role for the hemoprotein.

Effect of mutations on the p53 IRES RNA structure Implications for de-regulation of the synthesis of p53 isoforms

Earlier we have demonstrated the presence of internal ribosome entry site (IRES) within tumor suppressor p53 mRNA. Here we have mapped the putative secondary structure of p53-IRES RNA using information from chemical probing and nuclease mapping experiments. Additionally, the secondary structure of the IRES element of the wild-type RNA was compared with cancer-derived silent mutant p53 RNAs. These mutations might result in the conformational alterations of p53-IRES RNAs. The results also indicate decreased IRES activities of the mutants as compared to wild-type RNA. Further, it was observed that some of the cytoplasmic trans-acting factors, critical for enhancing IRES function, were unable to bind mutant RNAs as efficiently as to wild-type. Our results suggest that hnRNP C1/C2 binds to p53-IRES and siRNA mediated partial silencing of hnRNP C1/C2 showed appreciable decrease in IRES function and consequent decrease in the level of the corresponding p53 isoform. Interestingly mutant p53 IRES showed lesser binding with hnRNP C1/C2 protein. Finally, upon doxorubicin treatment, the mutant RNAs were unable to show enhanced p53 synthesis to similar extent compared to wild type. Taken together, these observations suggest that mutations occurring in the p53 IRES might have profound implications for de-regulation of its expression and activity.

Regulation of diacylglycerol kinase in rat brain membranes by docosahexaenoic acid

The effect of docosahexaenoic acid (DHA) on the diacylglycerol kinase (DG kinase) activity in rat brain membranes was investigated. DHA at 500 mu M concentration, stimulated the enzyme activity by about 2 fold. This effect was concentration-and time-dependent and was observed after very short periods of incubation (one min). DHA stimulation of DG kinase was observed only with rat brain membranes, and not with rat brain cytosol or rat liver membranes. Treating the rat brain membranes with phospholipase A(2) which released free fatty acids including DHA, significantly stimulated the DG kinase activity. It is concluded that DHA through its stimulatory effect on DG kinase may regulate the signalling events in growth-related situations in the brain such as synaptogenesis.

Optimal blood glucose regulation of diabetic patients using single network adaptive critics

Diabetes is a long-term disease during which the body's production and use of insulin are impaired, causing glucose concentration level to increase in the bloodstream. Regulating blood glucose levels as close to normal as possible leads to a substantial decrease in long-term complications of diabetes. In this paper, an intelligent online feedback-treatment strategy is presented for the control of blood glucose levels in diabetic patients using single network adaptive critic (SNAC) neural networks (which is based on nonlinear optimal control theory). A recently developed mathematical model of the nonlinear dynamics of glucose and insulin interaction in the blood system has been revised and considered for synthesizing the neural network for feedback control. The idea is to replicate the function of pancreatic insulin, i.e. to have a fairly continuous measurement of blood glucose and a situation-dependent insulin injection to the body using an external device. Detailed studies are carried out to analyze the effectiveness of this adaptive critic-based feedback medication strategy. A comparison study with linear quadratic regulator (LQR) theory shows that the proposed nonlinear approach offers some important advantages such as quicker response, avoidance of hypoglycemia problems, etc. Robustness of the proposed approach is also demonstrated from a large number of simulations considering random initial conditions and parametric uncertainties. Copyright (C) 2009 John Wiley & Sons, Ltd.

Genetic regulation of flower development

Flower development provides a model system to study mechanisms that govern pattern formation in plants. Most flowers consist of four organ types that are present in a specific order from the periphery to the centre of the flower. Reviewed here are studies on flower development in two model species: Arabidopsis thaliana and Antirrhinum majus that focus on the molecular genetic analysis of homeotic mutations affecting pattern formation in the flower. Based on these studies a model was proposed that explains how three classes of regulatory genes can together control the development of the correct pattern of organs in the flower. The universality of the basic tenets of the model is apparent from the analysis of the homologues of the Arabidopsis genes from other plant species

In vitro and in vivo regulation of assimilatory nitrite reductase from Candida utilis

The nitrate assimilation pathway in Candida utilis, as in other assimilatory organisms, is mediated by two enzymes: nitrate reductase and nitrite reductase. Purified nitrite reductase has been shown to be a heterodimer consisting of 58- and 66-kDa subunits. In the present study, nitrite reductase was found to be capable of utilising both NADH and NADPH as electron donors. FAD, which is an essential coenzyme, stabilised the enzyme during the purification process. The enzyme was modified by cysteine modifiers, and the inactivation could be reversed by thiol reagents. One cysteine was demonstrated to be essential for the enzymatic activity. In vitro, the enzyme was inactivated by ammonium salts, the end product of the path way, proving that the enzyme is assimilatory in function. In vivo, the enzyme was induced by nitrate and repressed by ammonium ions. During induction and repression, the levels of nitrite reductase mRNA, protein, and enzyme activity were modulated together, which indicated that the primary level of regulation of this enzyme was at the transcriptional level. When the enzyme was incubated with ammonium salts in vitro or when the enzyme was assayed in cells grown with the same salts as the source of nitrogen, the residual enzymatic activities were similar. Thus, a study of the in vitro inactivation can give a clue to understanding the mechanism of in vivo regulation of nitrite reductase in Candida utilis.

Regulation of progesterone biosynthesis in the human placenta by estradiol 17 beta and progesterone

Ex vivo addition of estradiol 17 beta to first trimester or term human placental minces caused a significant increase in the quantity of progesterone produced. Addition of an aromatase inhibitor, CGS 16949 A or the estrogen receptor antagonist, ICI 182780, significantly inhibited progesterone production confirming the role of estradiol 17 beta in the regulation of progesterone synthesis in human placenta. RU 486 and ZK 98299, which are antagonists of progesterone receptor, significantly modulated progesterone synthesis in the human placenta but exhibited paradoxical effects on the first trimester and term placenta We conclude that progesterone synthesis in the human placenta is regulated by estradiol 17 beta and progesterone. This is the first report providing evidence for autoregulation of progesterone synthesis in the human placenta.