Effects of Dietary Cholesterol on Pyroglutamyl Aminopeptidase Activity in Mouse Frontal Cortex, Pituitary, and Adrenal Glands

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.

Key words

Thyrotropin-Releasing Hormone Degrading Ectoenzyme - Dietary Lipids - Sex Differences - Pyrrolidon Carboxypeptidase

References

• 1 McDonald J K, Barret A J. Mammalian Proteases: A glossary and bibliography. London; Academic Press 1986
• 2 Browne P, O'Cuinn G. An evaluation of the role of a pyroglutamate aminopeptidase a post-proline cleaving enzyme and a post-proline dipeptidyl aminopeptidase each purified from the soluble fraction of guinea-pig brain in the degradation of thyroliberin in vitro.  Eur J Biochem. 1983;  137 75-87
• 3 O'Connor B, O'Cuinn G. Localization of a narrow-specificity thyroliberin-hydrolysing pyroglutamate aminopeptidase in synaptosomal membranes of guinea-pig brain.  Eur J Biochem. 1984;  144 271-278
• 4 Bauer K. Purification and characterization of the thyrotropin-releasing-hormone-degrading ectoenzyme.  Eur J Biochem. 1994;  224 387-396
• 5 Ramirez-Expósito M J, Martinez-Martos J M, Mayas M D, Garcia M J, Prieto I, Arechaga G, Ramirez M. Oleate linoleate and cholesterol differently modify aspartyl- and glutamyl-aminopeptidase activities in primary cultures of rat astrocytes.  Comp Biochem Physiol. 2001;  128 113-118
• 6 Ramirez-Expósito M J, Martinez-Martos J M, Prieto I, Alba F, Ramirez M. Angiotensinase activity in mice fed an olive oil-supplemented-diet.  Peptides. 2001;  22 945-952
• 7 Chui D H, Marotta J, Zang J S, Liu Y, Rao M L, Liu D S. Influence of high cholesterol feeding on the pattern and progression of experimental cerebral ischemia.  Biomed Pharmacoter. 1991;  45 409-415
• 8 Haque Z U, Mozaffar Z, Mozaffor Z. Importance of dietary cholesterol for the maduration of mouse brain myelin.  Biosci Biotechnol Biochem. 1992;  56 1351-1354
• 9 Oner P, Bekpinar S, Oz B. Alterations in some lipid components and Ca²⁺ ATPase activity in brain and rat fed an atherogenic diet.  Res Common Chem Pathol Pharmacol. 1991;  72 327-345
• 10 Eckert G P, Cairns N J, Maras A, Gattaz W F, Muller W E. Cholesterol modulates the membrane-disorder in effects of β-amyloid peptides in the hippocampus: Specific changes in Alzheimer's disease.  Dement Geriatr Cogn Disord. 2000;  11 181-186
• 11 Schwabe C, McDonald J K. Demonstration of a pyroglutamyl residue at the N-terminus of the B-chain of porcine relaxin.  Biochem Biophys Res Commun. 1977;  74 1501-1504
• 12 Bradford M M. A rapid and sensitive method for the quantification of microgram quantities of protein utilising the principle of protein-dye binding.  Anal Biochem. 1976;  72 248-254
• 13 Martinez J M, Ramirez M J, Prieto I, Alba F, Ramirez M. Sex differences and in vitro effects of steroids on serum aminopeptidase activity.  Peptides. 1998;  19 1637-1640
• 14 Martínez J M, Prieto I, Ramirez M J, Alba F, Ramírez M. Cholesterol and steroid action on aminopeptidases.  Biochem Soc Trans. 1997;  25 113S
• 15 Bauer K. Degradation and biological inactivation of thyrotropin releasing hormone (TRH): Regulation of the membrane-bound TRH-degrading enzyme from rat anterior pituitary by estrogens and thyroid hormones.  Biochimie. 1988;  70 69-74
• 16 Schomburg L, Bauer K. Regulation of the adenohypophyseal thyrotrophin-releasing hormone-degrading ectoenzyme by estradiol.  Endocrinology. 1997;  138 3587-3593
• 17 Thomson M. Molecular and cellular mechanisms used in the acute phase of stimulated steroidogenesis.  Horm Metab Res. 1998;  30 16-28
• 18 Baulieu E E, Robel P, Schumacher M. Neurosteroids: Beginning of the story.  Int Rev Neurobiol. 2001;  46 1-32
• 19 Huang Y S, Koba K, Horrobin D F, Sugano M. Interrelation between dietary protein cholesterol and n-6 polyunsaturated fatty acid metabolism.  Prog Lipid Res. 1993;  32 123-137
• 20 Yehuda S, Rabinovitz S, Carasso R, Mostofsky D. Fatty acids and brain peptides.  Peptides. 1998;  19 407-419
• 21 Ramírez-Expósito M J, Martínez-Martos J M, Mayas M D, Tsuboyama G, Prieto I, Arechaga G, Ramírez M. Depolarization increases pyroglutamyl aminopeptidase activity in rat frontal cortex synaptosomes inhibitory effect of aminoglycoside antibiotics neomycin and kanamycin.  Rev Neurol. 2000;  30 1022-1026
• 22 Brunner J, Bronisch T. Neurobiological correlaters of suicidal behavior.  Fortschr Neurol Psychiatr. 1999;  67 391-412
• 23 Sattin A, Kubek M J, Low W C, Staley C J, Simon J R. Some regional anatomical relationships of TRH to 5HT in rat limbic forebrain.  Neurochem Res. 1992;  17 469-473
• 24 Pijl H, Koppeschaar H P, Willekens F L, Frolich M, Meinders A E. The influence of serotonergic neurotransmission on pituitary hormone release in obese and non-obese females.  Acta Endocrinol Copenh. 1993;  128 319-324
• 25 Mayas M D, Ramírez-Expósito M J, Garcia M J, Tsuboyama G, Ramirez M, Martínez-Martos J M. Calcium-dependent modulation by ethanol of mouse synaptosomal pyroglutamyl aminopeptidase activity under basal and K⁺-stimulated conditions.  Neurosci Lett. 2000;  293 199-202