Article

Effects of dietary cholesterol on pyroglutamyl aminopeptidase activity in mouse frontal cortex, pituitary, and adrenal glands.

Unit of Physiology, Department of Health Sciences, Faculty of Experimental and Health Sciences, University of Jaén, Spain.
Hormone and Metabolic Research (Impact Factor: 2.04). 09/2002; 34(8):431-4. DOI: 10.1055/s-2002-33600
Source: PubMed

ABSTRACT Pyroglutamyl aminopeptidase (pGluAP) is an omega peptidase that hydrolyzes biologically active peptides, such as thyrotropin-releasing hormone (TRH), with neuronal and extraendocrine functions. We analyzed the effects of a cholesterol-enriched diet on soluble and membrane-bound pGluAP activity in frontal cortex, pituitary and adrenal glands of male and female mice using fluorimetric assays. Significant increases were observed in soluble pGluAP activity in the frontal cortex and adrenal glands in males and in the pituitary in females. Membrane-bound pGluAP activity was increased in the frontal cortex and pituitary of males and females after the mice were fed a cholesterol-enriched diet. These increases may produce changes in the metabolism of endogenous substrates, including TRH, which may be related to alterations in its neuromodulator functions and to the possible relationship between TRH and other neurotransmitter systems.

0 Followers
 · 
43 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Pyrrolidon carboxypeptidase is an omega-peptidase that hydrolyses N-terminal pyroglutamyl residues from biologically active peptides such as gonadotropin-releasing and thyrotrophin-releasing hormones. We previously described a decrease in both rat and human pyrrolidon carboxypeptidase activity with breast cancer, suggesting that gonadotropin-releasing hormone may be an important local intracrine, autocrine and/or paracrine hormonal factor in the pathogenesis of breast cancer while playing a role in the tumoral process. However, the other susceptible substrate of pyrrolidon carboxypeptidase, thyrotrophin-releasing hormone, may also be modified with breast cancer, supporting an association between breast cancer and thyroid disorders. The present work analyses soluble and membrane-bound pyrrolidon carboxypeptidase activities in the hypothalamus-pituitary-thyroid and hypothalamus-pituitary-ovary axes in N-methyl nitrosourea-induced breast cancer in rats. Our aim was to determine the possible relationship between gonadotropin-releasing hormone and thyrotrophin-releasing hormone regulation through pyrrolidon carboxypeptidase activity. We propose that pyrrolidon carboxypeptidase activity dysregulation at various local and systemic levels may participate in the initiation, promotion and progression of breast cancer induced in rat by N-methyl nitrosourea through the increase in gonadotropin-releasing hormone. Since pyrrolidon carboxypeptidase activity also acts on thyrotrophin-releasing hormone, the dysregulation of this enzyme's activity could indirectly affect hypothalamus-pituitary-thyroid axis function, and thus potentially represent a link between the diseases of thyroid and breast cancer.
    Hormone and Metabolic Research 03/2005; 37(2):74-8. DOI:10.1055/s-2005-861158 · 2.04 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The synthesis, spectroscopic (IR, 1H and 13C NMR, UV-Vis-NIR, EPR), magnetic measurements and biological studies of a number of complexes of Co(II), Ni(II), Cu(II), Zn(II), Cd(II), Au(III) and Hg(II) of the Schiff base derived from the 1:2 condensation of 2,6-diformyl-4-methylphenol and 5-aminouracil, ((5-[[(3-[[(2,4-dioxopyrimidin-5(1H,3H)-yl)imino]methyl]-2-hydroxy-5-methylphenyl)methylene]amino]pyrimidine-2,4(1H,3H)-dione, hereafter denoted as BDF5AU) are reported. In all cases, the complexes appear to be monomeric. The deprotonated ligand in the phenolic oxygen atom shows a tridentate coordination mode through the two azomethine nitrogen atoms and the phenolic oxygen atom. The coordination of the neutral ligand takes place through the phenolic oxygen atom and one azomethine nitrogen atom and the carbonylic oxygen atom in fourth position of one uracil ring. The biological properties of some perchlorate complexes on the activity of some neutral, acid, basic and omega aminopeptidases (AP) are assayed, demonstrating a general inhibitory effect. Neutral and basic AP are mainly inhibited by Cu(II), Ni(II) and Cd(II) complexes, although tyrosyl-AP is activated by Zn(II) complex. Glutamyl-AP but not aspartyl-AP is inhibited by all the complexes assayed excepting Zn(II) complex. Finally, omega AP is inhibited by Ni(II) and Cd(II) complexes.
    Journal of Inorganic Biochemistry 05/2003; 94(4):326-34. DOI:10.1016/S0162-0134(03)00025-4 · 3.27 Impact Factor