Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of apoptotic signaling proteins for long-lived neurons in the mature brain is poorly understood. Recently, we have shown that water deprivation leads to the activation of vasopressin (VP) secretion and expression of Bcl-2 and caspase-9 apototic proteins in the hypothalamus of the rat brain. In the present work, we continued to study a possible relationship between the functional activity of neurosecretory cells of the hypothalamus and apoptosis related proteins. We found that water deprivation leads to simultaneous activation of synthesis of VP and p53 and Bcl-2 apoptotic proteins in the mouse brain. To study a possible effect of apoptotic proteins on the functional state of hypothalamic neurons, the VP and tyrosine hydroxylase (TH) synthesis were analyzed in p53, p21(Waf1/Cip1) and Bcl-2 deficient mice. Loss of p53 and Bcl-2 significantly reduced VP synthesis in paraventricular and supraoptic nuclei and TH expression in arcuat, periventricular and zona incerta nuclei of the hypothalamus. Surprisingly, in contrast with the loss of p53, the inactivation of p21(Waf1/Cip1) up-regulates the expression of VP and TH. These data indicate that p53, p21(Waf1/Cip1) and Bcl-2 proteins, besides affecting cell cycle, tumor suppression and apoptosis, may act as modulators of neurosecretory activity of hypothalamic neurons; however, this problem remains to be determined more detailed.
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PMID:Apoptotic signaling proteins: possible participation in the regulation of vasopressin and catecholamines biosynthesis in the hypothalamus. 1613 24

Hypothalamic magnocellular neurons (MCNs) are highly vulnerable to axotomy-induced cell death in vivo and in vitro. In this study, we determined whether the anti-apoptotic agent Bcl-xL, a member of the Bcl-2 family which prevents programmed cell death in the central nervous system, can rescue oxytocin (OT) and vasopressin (VP) MCNs in the supraoptic nucleus (SON) in organotypic culture. We found that the novel, membrane permeant form of Bcl-xL that we employed in these studies protected both OT and VP MCNs from degeneration as long as the Bcl-xL was present in the medium. In contrast, z-VAD-fmk, an inhibitor of caspases that are involved in apoptosis, was less effective in that it significantly rescued OT MCNs (P < 0.01) but not VP MCNs (P > 0.09). Unlike the Bcl-xL, Z-VAD-fmk's effectiveness in reducing MCN cell death was not sustained for the full 15 days in vitro.
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PMID:Bcl-xL and caspase inhibition increase the survival of rat oxytocin and vasopressin magnocellular neurons in organotypic culture. 1662 98

Tyrosine kinase receptor HER2/neu plays an important role in a number of processes including carcinogenesis. The oncogenic characteristics of HER2/neu are associated with its ability to affect a variety of apoptotic pathways creating, this way, an antiapoptotic environment in the cells overexpressing this protein. The aim of our work was to investigate the features of apoptosis regulation in hypothalamic neurosecretory cells of HER2/neu transgenic mice in aging. We detected the apoptosis protein expression (Bax, c-Raf) in comparison with apoptosis level and functional activity (vasopressin concentration) in neuroendocrine system. Besides, we studied the level of 17beta-estradiol in blood plasma. 17beta-estradiol is one of possible antiapoptotic factors in neurons. We show that the apoptosis of neuroendocrine cells increases in aged wild type mice, but not in HER2/neu ones. Recently we obtained that the mechanism of apoptosis suppression in transgenic mice is the block of p53-dependent apoptosis cascade, and it is the cause of caspadse-8 decrease and dysregulation of Bcl-2 and Mcl-1 antiapoptotic protein synthesis. In this study it has been shown that Bax concentration decreases and c-Raf-1 expression does not change. 17beta-estradiol does not decrease in plasma of aged transgenic mice and it is the factor, which can play a positive role in neuroendocrine cells survival. Besides, the vasopressin synthesis increases in young and old HER2 mice. These facts result in the increased survival of neurosecretory cells in old transgenic mice.
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PMID:[Apoptosis regulation in hypothalamic neurosecretory cells of HER2/neu transgenic mice in ontogenesis]. 1838 7

In this study we examined whether in vivo treatments with Bcl-2 inhibitor HA14-1 can affect the function of vasopressinergic system of rat. HA14-1 is a novel organic compound that has micromolar affinity for Bcl-2 and Bcl-xL and acts as a mimetic of BH3-only proteins by antagonizing the anti-apoptotic Bcl-2 proteins and triggering Bax-dependent apoptosis. We found that intrahypothalamic injections of HA14-1 did not induce apoptosis of vasopressin (VP) cells of supraoptic nucleus, but led to activation of VP synthesis and release, resulting in decreased diuresis. Our data has also demonstrated that injections of HA14-1 increased phospho-MEK1/2, phospho-CREB and phospho-Elk-1 levels in magnocellular neurons. Thus we propose that injections of HA14-1 into the hypothalamus do not lead to neuronal death, but change the functional activity of VP neurons of hypothalamus centres.
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PMID:Effects of selective Bcl-2 inhibitor HA14-1 treatments on functional activity of magnocellular vasopressinergic neurons of rat hypothalamus. 1843 13

In most vertebrates studied, males have more vasopressin (VP) cells in the bed nucleus of the stria terminalis, or homologous vasotocin cells in nonmammalian species, than females. Previous research excluded differential cell birth and migration as likely mechanisms underlying this difference, leaving just differential cell death and phenotypic differentiation of existing cells. To differentiate between these remaining possibilities, we compared VP cell number in wild-type mice vs. mice overexpressing the anti-cell death factor, Bcl-2. All animals were gonadectomized in adulthood and given testosterone capsules. Three weeks later, brains were processed for in situ hybridization to identify VP cells. Bcl-2 overexpression increased VP cell number in both sexes but did not reduce the sex difference. We repeated this experiment in mice with a null mutation of the pro-cell death gene, Bax, and obtained similar results; cell number was increased in Bax(-/-) mice of both sexes, but males had about 40% more VP cells, regardless of Bax gene status. Taken together, cell death is unlikely to account for the sex difference in VP cell number, leaving differentiation of cell phenotype as the most likely underlying mechanism. We also used immunocytochemistry to examine VP projections in Bcl-2-overexpressing mice. As expected, males showed denser VP-immunoreactive fibers than females in the lateral septum, a projection area of the bed nucleus of the stria terminalis. However, even though Bcl-2 overexpression increased VP cell number, it did not affect fiber density. Thus, a compensatory mechanism may control total septal innervation regardless of the number of contributing cells.
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PMID:Sexual differentiation of vasopressin innervation of the brain: cell death versus phenotypic differentiation. 1849 46

To study character of effect of apoptosis signal proteins on activities of neurosecretory cells and neurons of rat hypothalamus, pharmacologic inhibitors of proapoptotic protein p53 Pifithrin-alpha and antiapoptotic protein Bcl-2 HA14-1 were injected into the hypothalamus. Activation of vasopressinergic neurosecretory cells at administration of the blocker Bcl-2 HA14-1 was shown: there were observed an increase of vasopressin mRNA in neurons of hypothalamus supraoptical and paraventricular nuclei, a decrease of the immunoreactive vasopressin content in posterior pituitary, and reduction of diuresis. Inactivation of p53 inhibited release of vasopressin from hypothalamus cell bodies, which is indicated by an elevated content of immunoreactive vasopressin in neurosecretory cell bodies with its unchanged synthesis, a decrease of the neurohormone content in the posterior pituitary, and an increase of diuresis rate. Activation of vasopressinergic neurons of the suprachiasmatic nucleus was also shown. Administration of the blocker Bcl-2 has been revealed to decrease functional activity both of dopaminergic neurons (Zona Incerta) and of dopaminergic neurosecretory cells (arcuate nucleus), in which a decrease of the tyrosine hydroxylase content was observed. The p53 inactivation also led to a decrease of activity of dopaminergic neurosecretory cells of arcuate nucleus, whereas activity of the proteins Zone Incerta did not change. Thus, it has been shown that a change of the apoptotic protein content in vasopressinergic and dopaminergic neurons and neurosecretory cells leads to a change of their functional activity, the character and possibly mechanisms of effects of apoptotic proteins on activities of vasopressin- and dopaminergic cells being different.
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PMID:[Effect of apoptosis proteins on function of vasopressin- and dopaminergic hypothalamic neurons]. 1872 20

The hormonal control of cell death is currently the best-established mechanism for creating sex differences in cell number in the brain and spinal cord. For example, males have more cells than do females in the principal nucleus of the bed nucleus of the stria terminalis (BNSTp) and spinal nucleus of the bulbocavernosus (SNB), whereas females have a cell number advantage in the anteroventral periventricular nucleus (AVPV). In each case, the difference in cell number in adulthood correlates with a sex difference in the number of dying cells at some point in development. Mice with over- or under-expression of cell death genes have been used to test more directly the contribution of cell death to neural sex differences, to identify molecular mechanisms involved, and to determine the behavioural consequences of suppressing developmental cell death. Bax is a pro-death gene of the Bcl-2 family that is singularly important for apoptosis in neural development. In mice lacking bax, the number of cells in the BNSTp, SNB and AVPV are significantly increased, and sex differences in total cell number in each of these regions are eliminated. Cells rescued by bax gene deletion in the BNSTp express markers of differentiated neurones and the androgen receptor. On the other hand, sex differences in other phenotypically identified populations, such as vasopressin-expressing neurones in the BNSTp or dopaminergic neurones in AVPV, are not affected by either bax deletion or bcl-2 over-expression. Possible mechanisms by which testosterone may regulate cell death in the nervous system are discussed, as are the behavioural effects of eliminating sex differences in neuronal cell number.
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PMID:Control of cell number in the sexually dimorphic brain and spinal cord. 1920 22

Echinocystic acid (EA), a pentacyclic triterpene, was isolated and identified from the fruits of Gleditsia sinensis Lam. The protective effects of EA were evaluated in rat models with acute myocardial ischemia induced by isoproterenol and vasopressin. In the electrocardiogram of anesthetized rats, EA prevented the ST-segment depression induced by isoproterenol or vasopressin in a dose-dependently manner. Furthermore, the mRNA expression of Bcl-2 was analyzed by RT-PCR. EA shows an elevation of Bcl-2 mRNA level in infarcted tissue induced by isoproterenol in rats. These results demonstrated for the first time EA has a cardioprotective effect and may be a natural drug.
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PMID:Protective effects of echinocystic acid isolated from Gleditsia sinensis Lam. against acute myocardial ischemia. 1957 79

Tumor necrosis factor (TNF) participates in regulation of many processes including carcinogenesis and apoptosis. However, at present, there are practically absent the works on peculiarities of regulation of apoptosis in tnf-knockout (tnf-/-) mice. These mice develop without morphological abnormalities, but they seem to have disturbances of many biological processes, such as inflammation, programmed cell death, etc. Therefore, the goal of our work was to study possible pathways of regulation of apoptosis in the absence of TNF in neurosecretory cells (NSC) of young and old mice. For this purpose, we determined immunohistochemically expression of apoptosis markers caspase-8, -9. Bax, Bcl2, Mcl1, neuropeptide vasopressin, and the apoptosis level in hypothalamus in tnf-knockout mice of different ages as compared with mice with unchanged level of TNF synthesis. It was shown that the apoptosis activation observed during aging did not depend on the tnf gene, and apoptosis at aging was caspase-dependent. It has been revealed that at aging in mouse NSC the external cell death pathway with participation of caspase-8 is activated. The pathways mediating cell death in different neurosecretory centers at aging are different. Thus, in supraoptic nucleus (SON), in all studied animal groups, animal groups, an important cause of the NSC apoptosis is Bax. In paraventricular nucleus (PVN), of the greater importance is a decrease of the antiapoptotic protection. Hence, misbalance of synthesis of proteins of the Bcl-2 family plays an important role in development of senescent apoptosis.
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PMID:[Ontogenetic peculiarities of regulation of apoptosis in hypothalamic neurosecretory cells in thf-knockout mice]. 1988

The antiapoptotic protein Bcl-2 has various functions besides its role in protecting cells from apoptosis. Previous studies have demonstrated that Bcl-2 recruits ERK1/2 and/or CREB to initiate different transcription program in the regulation of various neuronal activities as well as axonal growth. Recently we reported that Bcl-2 can participate in the regulation of synthesis and secretion of vasopressin of rat hypothalamic magnocellular nuclei. In thise study we have investigated the inhibition of Bcl-2 on vasopressin expression in magnocellular neurons of hypothalamic supraoptic nuclei. The experiments were done on short-term incubated rat hypothalamic slices containing supraoptic nuclei. Our data demonstrated that in vitro inhibition of Bcl-2 by HA14-1 prevented CREB translocation into the cell nuclei and significantly decreased vasopressin mRNA level and enhanced contents of vasopressin protein in magnocellular neurons in supraoptic nucleus. Our results indicate that CREB-dependent vasopressin gene transcription in the hypothalamic magnocellular neurons can be regulated by Bcl-2.
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PMID:[Role of Bcl-2 in the regulation of creb activity and vasopressin expression in the hypothalamic neurons of rats]. 2301 26


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