ABSTRACT
Membrane extracellular microvesicles serve as carriers of a wide range of molecules, the most important among these are proteins, lipids, and nucleic acids. Cytotoxic proteins of natural killer cells play a key role in the realization of their cytolytic functions. An important stage in understanding of the distant communication of cells and mechanisms of its regulation is analysis of the proteome composition of microvesicles. We studied the proteomic composition of microvesicles produced by NK-92 natural killer cells. Granzyme A, a specific protein of cytotoxic cells, has been identified in the microvesicles by QTOF-mass spectrometry. It was shown that heat shock proteins, components of the ubiquitin-proteasome system, enzymes of protein biosynthesis and energy metabolism, nuclear and serum proteins, as well as cytoskeleton proteins are associated with the microvesicles.
Subject(s)
Killer Cells, Natural/metabolism , Mass Spectrometry/methods , Proteome/analysis , Cell Line , Cell-Derived Microparticles , Electrophoresis, Gel, Two-Dimensional , Humans , Proteomics/methodsABSTRACT
Effects of prenatal hyperhomocysteinemia on hypothalamic regulation of estrous cycles were studied in female rats. In mature rats exposed to prenatal hyperhomocysteinemia, changes in the catecholamine content in hypothalamic areas responsible for the formation of the preovulatory surge of gonadotropin-releasing hormone were revealed: the level of norepinephrine in the medial preoptic area decreased and concentration of dopamine in the median eminence with arcuate nuclei increased. Administration of melatonin attenuated the observed changes, which can be related to neuroprotective effects of this hormone determined by its antioxidant properties.
Subject(s)
Antioxidants/pharmacology , Estrous Cycle/drug effects , Hyperhomocysteinemia/prevention & control , Melatonin/pharmacology , Neuroprotective Agents/pharmacology , Prenatal Exposure Delayed Effects/prevention & control , Animals , Arcuate Nucleus of Hypothalamus/drug effects , Arcuate Nucleus of Hypothalamus/metabolism , Arcuate Nucleus of Hypothalamus/physiopathology , Catecholamines/metabolism , Female , Gonadotropin-Releasing Hormone/metabolism , Hyperhomocysteinemia/chemically induced , Hyperhomocysteinemia/metabolism , Hyperhomocysteinemia/physiopathology , Luteinizing Hormone/metabolism , Median Eminence/drug effects , Median Eminence/metabolism , Median Eminence/physiopathology , Methionine/adverse effects , Methionine/metabolism , Norepinephrine/metabolism , Pregnancy , Prenatal Exposure Delayed Effects/chemically induced , Prenatal Exposure Delayed Effects/metabolism , Prenatal Exposure Delayed Effects/physiopathology , Preoptic Area/drug effects , Preoptic Area/metabolism , Preoptic Area/physiopathology , Progesterone/metabolism , Rats , Rats, WistarABSTRACT
This review covers present-day ideas of the female organism reproductive system neuroendocrine regulation in aging. The literature data on the key role of the hypothalamus in formation, organization and age-related decline of the reproductive function in both mammals and humans are considered in detail. Special focus is on catecholamines, peptides and other biologically active compounds acting in these processes. The authors discuss data showing interaction between the suprachiasmatic nuclei of the hypothalamus and the pineal gland synchronizing circadian and diurnal rhythms of gonadotropine-releasing hormone being normally synthesised and secreted during the reproductive period, but failing in aging or under the influence of neurotoxic compounds. Molecular mechanisms of ovarian cycle hypothalamic regulation impairment and possible ways of its correction by means of melatonin and peptide preparations from the pineal gland are described. The data presented may be of utility to prevent premature aging of reproductive function.
