Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A method of isolating pure fractions of 4 alpha-methyl-5 alpha-ergosta-8,24(28)-dien-38-ol for sterol intermediate studies is described. Starvation cultures of Neurospora crassa readily incorporate exogenous mevalonic acid into the sterol ester fraction. Isolation involves a simple solvent extraction and two chromatograms. Only the ester fraction yielded the required purity. Radioactive 4 alpha-methyl-5 alpha-ergosta-8,24(28)-dien-3 beta-ol is readily produced from DL-[2-14C] mevalonic acid.
Steroids 1979
PMID:Isolation of 4 alpha-methyl-5 alpha-ergosta-8,24(28)-dien-3 beta-ol from ester fractions of nutritionally deprived Neurospora crassa. 16 33

Induction of apoptosis is a feature of the anti-tumor effects of certain vitamin D analogs. The aim of this study was to identify if common effectors are involved in cell death mediated by serum starvation, vitamin D analogs and tumor necrosis factor (TNF) alpha in 3 human breast cancer cell lines: MCF-7, T47-D and Hs578T. Incubation of cells in serum-free medium induced apoptosis as assessed by loss of cell viability and increased DNA fragmentation. Addition of IGF-I (30 ng/ml) protected against loss of cell viability in MCF-7 cells and co-treatment with two synthetic analogs (CB1093 and EB1089, 50 nM for 4 days) prevented these anti-apoptotic effects of IGF-I. Pretreatment of MCF-7 and Hs578T cells with the vitamin D analogs substantially potentiated the cytotoxic effects of TNFalpha. This cytokine was not cytotoxic for T47-D cells but co-incubation with CB1093 led to loss of cell viability. Potentiation by CB1093 of TNFalpha-induced apoptosis in MCF-7 cells was accompanied by increased activation of cytosolic phospholipase A2 and arachidonic acid release, which was partially inhibited by AACOCF3, a specific cPLA2 inhibitor. The broad-spectrum caspase inhibitor z-VAD-fmk prevented TNFalpha but not CB1093 mediated cell death and activation of cPLA2. Serum starvation induced apoptosis was accompanied by cPLA2 activation, which was inhibited by IGF-I and by z-VAD-fmk. However, the ability of these agents to suppress cPLA2 activation was abrogated by co-treatment with CB1093, suggesting a role for arachidonic acid release in the caspase-independent mechanism by which vitamin D analogs prevent the protective effects of IGF-I on breast cancer cell survival.
Steroids
PMID:Interaction of vitamin D analogs with signaling pathways leading to active cell death in breast cancer cells. 1117 39

Many studies have demonstrated the nuclear forms of steroid receptors and their activities, while fewer investigators have identified and described the membrane forms of these receptors. Our immuno-identification approaches for the qualitative and quantitative comparison of the membrane form of the estrogen receptor-alpha (mER alpha) to its nuclear counterpart now allow us to address questions about the comparative levels and regulation of these receptor forms. ER alpha-specific antisense oligonucleotides eliminate mER alpha expression, while only mildly reducing the nuclear ER alpha. Success of immuno-identification for the mER alpha is very sensitive to different fixation protocols, affecting cell permeability (and thus distinction from the intracellular form) and differential epitope preservation. All such identifications must be accompanied by proof of cell membrane integrity and focal plane assessments. The mER alpha expression on selected cells declines rapidly with cell passage number and cell density. Expression of mER alpha is enhanced by serum starvation and selection for specific phases of the cell cycle. The hinge region of the protein is sensitive to ligand-induced epitope masking and to antibody-induced changes in receptor-mediated responses. Responsive cells are often diluted within cell populations by loss of the membrane receptor form. The bimodality of the rapid estrogen action, with inhibitory doses between picomolar and nanomolar stimulatory concentrations, requires detailed dose-response curves. Finally, responsive cells can be lost from assays, as upon estrogen treatment they rapidly round up and leave the substrates to which they are attached. These regulatory phenomena demonstrate that levels of the membrane form of the estrogen receptor are very dynamic.
Steroids 2002 May
PMID:The dynamic and elusive membrane estrogen receptor-alpha. 1196 Jun 18

Ovarian cell death is an essential process for the homeostasis of ovarian function in human and other mammalian species. It ensures the selection of the dominant follicle and the demise of excess follicles. In turn, this process minimizes the possibility of multiple embryo development during pregnancy and assures the development of few, but healthy embryos. Degeneration of the old corpora lutea in each estrous/menstrual cycle by programmed cell death is essential to maintain the normal cyclicity of ovarian steroidogenesis. Although there are multiple pathways that can determine cell death or survival, crosstalk among endocrine, paracrine and autocrine factors, as well as among protooncogenes, tumor suppressor genes, survival genes and death genes, plays an important role in determining the fate of ovarian somatic and germ cells. The establishment of immortalized rat and human steroidogenic granulosa cell lines and the investigation of pure populations of primary granulosa cells allows systematic studies of the mechanisms that control steroidogenesis and apoptosis in granulosa cells. We have discovered that during initial stages of granulosa cell apoptosis progesterone production does not decrease. In contrast, we found that it is elevated up to 24h following the onset of the apoptotic stimuli exerted by starvation, cAMP, p53 or TNF-alpha stimulation, before total cell collapse. These observations raise the possibility for an alternative unique apoptotic pathway, one not involving mitochondrial Cyt C release associated with the destruction of mitochondrial structure and steroidogenic function. Using mRNA from apoptotic cells and affymetrix DNA microarray technology we discovered that granzyme B, a protease that normally resides in T cytotoxic lymphocytes and natural killer cells of the immune system is expressed and activated in granulosa cells. Thus, the apoptotic signals could bypass mitochondrial signals for apoptosis, which can preserve their steroidogenic activity until complete cell destruction. This unique apoptotic pathway assures cyclicity of estradiol and progesterone release in the estrous/menstruous cycle even during the initial stages of apoptosis.
Steroids 2003 Nov
PMID:Steroidogenesis and apoptosis in the mammalian ovary. 1466 78

Apoptosis induced by oxidized low-density lipoproteins (oxLDL) and tumor necrosis factor-alpha (TNF-alpha) is believed to contribute to atherosclerosis and vascular dysfunction. Estrogen treatment reduces apoptosis due to TNF-alpha and we hypothesized that it would also reduce apoptosis due to oxLDL. We also explored the anti-apoptotic mechanisms. We used early passage human umbilical vein endothelial cells (HUVEC) grown in steroid-depleted, red phenol-free medium. Cells were synchronized by starvation for 6h and then treated with oxLDL (75microg/ml) or TNF-alpha (20ng/ml) in the presence of 17-beta-estradiol (E2) (20nM). Apoptosis was analyzed by flow cytometry and caspase-3 cleavage. We also assessed expression of Bcl-2 and Bcl-xL and phosphorylation of BAD. At 6h TNF-alpha induced apoptosis but oxLDL did not; E2 did not affect this TNF-alpha induced apoptosis and there was no change in Bcl-2 or Bcl-xL expression. At 24h both TNF-alpha and oxLDL increased apoptosis and E2 reduced the increase. E2 also increased expression of the anti-apoptotic Bcl-2 and Bcl-xL and increased phosphorylation of proapoptotic BAD which reduces its proapoptotic activity at 1h. However at 24h there was also an increase in total BAD so that the proportion of phosphorylation of BAD decreased. oxLDL induced apoptosis occurs later than that of TNF-alpha. E2 decreased this late phase apoptosis and this likely requires the production of anti-apoptotic proteins.
Steroids 2008 Jan
PMID:Estrogen decreases TNF-alpha and oxidized LDL induced apoptosis in endothelial cells. 1793 19

Granulosa cells proliferate, differentiate, and undergo apoptosis throughout follicular development. Previous studies have demonstrated that stimulation of progesterone production is accompanied by caspase-3 activation. Moreover, we previously reported that arsenic enhanced caspase-3 activity coupled with progesterone production. Inhibition of caspase-3 activity can significantly inhibit progesterone production induced by arsenic or follicle-stimulating hormone (FSH). Here, we report that serum starvation induces caspase-3 activation coupled with augmentation of progesterone production. Serum starvation also increased the levels of cytochrome P450 cholesterol side chain cleavage enzyme (P450scc) and steroidogenic acute regulatory (StAR) protein, both of which may contribute to progesterone synthesis in preovulatory granulosa cells. Inhibition of caspase-3 activity resulted in a decrease in progesterone production. Deactivation of caspase-3 activity by caspase-3 specific inhibitor also resulted in decreases in P450scc and StAR expression, which may partly contribute to the observed decrease in progesterone production. Our study demonstrates for the first time that progesterone production in preovulatory granulosa cells is required for caspase-3 activation in a serum starvation model. Inhibition of caspase-3 activity can result in decreased expression of the steroidogenic proteins P450scc and StAR. Our work provides further details on the relationship between caspase-3 activation and steroidogenesis and indicates that caspase-3 plays a critical role in progesterone production by granulosa cells.
Steroids 2012 Nov
PMID:Progesterone production requires activation of caspase-3 in preovulatory granulosa cells in a serum starvation model. 2296 62

Organisms respond to various environmental stressors by modulating physiology and behavior to maintain homeostasis. Steroids and catecholamines are involved in the highly conserved signaling pathways crucial for mounting molecular and cellular events that ensure immediate or long-term survival under stress conditions. The insect dopamine/ecdysteroid receptor (DopEcR) is a dual G-protein coupled receptor for the catecholamine dopamine and the steroid hormone ecdysone. DopEcR acts in a ligand-dependent manner, mediating dopaminergic signaling and unconventional "nongenomic" ecdysteroid actions through various intracellular signaling pathways. This unique feature of DopEcR raises the interesting possibility that DopEcR may serve as an integrative hub for complex molecular cascades activated under stress conditions. Here, we review previously published studies of Drosophila DopEcR in the context of stress response and also present newly discovered DopEcR loss-of-function phenotypes under different stress conditions. These findings provide corroborating evidence that DopEcR plays vital roles in responses to various stressors, including heat, starvation, alcohol, courtship rejection, and repeated neuronal stimulation in Drosophila. We further discuss what is known about DopEcR in other insects and DopEcR orthologs in mammals, implicating their roles in stress responses. Overall, this review highlights the importance of dual GPCRs for catecholamines and steroids in modulating physiology and behavior under stress conditions. Further multidisciplinary studies of Drosophila DopEcR will contribute to our basic understanding of the functional roles and underlying mechanisms of this class of GPCRs.
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PMID:Significance of DopEcR, a G-protein coupled dopamine/ecdysteroid receptor, in physiological and behavioral response to stressors. 3195 16