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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors evaluated the effects of stimulation (by serum, wounding, and three peptide growth factors: fibroblast growth factor [FGF], insulin, and transforming growth factor-beta [TGF-beta 1]) on the expression of the protein product of the immediate early gene, c-fos in bovine corneal endothelial (BCE) cells. These results were compared with those of cells which were made quiescent by serum starvation. They also examined the effect of these same growth factors or wounding on DNA synthesis. Quiescent cells expressed low levels of c-fos protein. Serum was the most potent stimulator, whereas FGF and insulin were modest stimulators. TGF-beta 1 did not significantly stimulate c-fos protein production. The results from DNA synthesis were different. Serum and FGF were still the most potent stimulators; insulin and TGF-beta 1 were weak stimulators. These data suggest that growth factors induce c-fos protein in BCE cells and that this may in part regulate the downstream event, cellular proliferation. Further investigation into the regulation of this and other protooncogene products may provide insight into the mechanisms which modulate corneal endothelial cell growth in humans.
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PMID:Fos expression and growth regulation in bovine corneal endothelial cells. 142 6

Anorexia nervosa is a serious eating disorder characterized by extreme weight loss and abnormalities of the neuroendocrine and immune systems. To determine the potential role of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and transforming growth factor-beta (TGF-beta) in anorexia nervosa, serum concentrations of these cytokines were measured in patients with anorexia nervosa during starvation and after weight gain. Serum IL-6 and TGF-beta concentrations were both significantly elevated during starvation and returned to levels comparable to those of normal-weight controls by the end of therapy. In contrast, serum TNF-alpha levels were undetectable in all patients and controls. Cytokines may play previously unsuspected roles in anorexia nervosa and its complications.
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PMID:Role of interleukin-6 and transforming growth factor-beta in anorexia nervosa. 789 47

The bone morphogenetic protein (BMP) family is a conserved group of signalling molecules within the transforming growth factor-beta (TGF-beta) superfamily. This group, including the Drosophila decapentaplegic (dpp) protein and the mammalian BMPs, mediates cellular interactions and tissue differentiation during development. Here we show that a homologue of human BMPs controls a developmental switch in the life cycle of the free-living soil nematode Caenorhabditis elegans. Starvation and overcrowding induce C. elegans to form a developmentally arrested, third-stage dauer larva. The daf-4 gene, which acts to inhibit dauer larva formation and promote growth, encodes a receptor protein kinase similar to the daf-1, activin and TGF-beta receptor serine/threonine kinases. When expressed in monkey COS cells, the daf-4 receptor binds human BMP-2 and BMP-4. The daf-4 receptor is the first to be identified for any growth factor in the BMP family.
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PMID:The daf-4 gene encodes a bone morphogenetic protein receptor controlling C. elegans dauer larva development. 841 26

Contact is a vital mechanism used by cells to interact with their environment. Contact with living and nonliving elements adjacent to a cell is the basis for many common biological events ranging from growth regulation to metastasis to embryonic pattern formation. We describe the cloning and characterization of a novel density-regulated protein (drp) whose expression is increased in cultured cells at high density compared with cells at low density. A drp cDNA was isolated from the human teratocarcinoma cell line PA-1. Northern analysis with a drp probe revealed transcripts of 2.8 and 3.2 kb. The drp RNA was expressed in a variety of tissues, with the highest amounts in skeletal and cardiac muscle. Using antipeptide antisera, increasing amounts of a 70-kDa protein were detected using several experimental approaches in several cells lines as cell density is increased. Conditioned medium from high-density cells was unable to induce expression of drp in cells growing at low density. Similarly, growth arrest by serum starvation or transforming growth factor-beta (TGF-beta) treatment failed to elicit drp expression. We conclude that drp is a novel protein whose expression is increased at high cell density but not growth arrest.
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PMID:drp, a novel protein expressed at high cell density but not during growth arrest. 962 87

Macrophage migration inhibitory factor (MIF) is a cytokine that mediates inflammatory processes in a variety of tissues. In this study, we examined the expression of MIF mRNA in the mouse osteoblastic cell line MC3T3-E1, whose proliferation is promoted by various growth factors. In the subconfluent state, transforming growth factor-beta, basic fibroblast growth factor, insulin-like growth factor-II, and fetal calf serum markedly upregulated MIF mRNA expression. The upregulation of MIF mRNA was less extensive when the cells were stimulated by the same growth factors in the overconfluent state. We also investigated the expression of MIF mRNA through a whole cell cycle from G0 phase when the osteoblastic cells were synchronized by serum starvation. The MIF mRNA expression, which gradually increased from the G0 and reached its maximum at the S phase, was nonperiodic. Moreover, human recombinant MIF upregulated the expression of urokinase plasminogen activator inhibitor-1 (PAI-1) precursor mRNA in human osteoblastic Saos-2 cells. Plasminogen activator (PA) is known to play an important role in bone metabolism, for example, in activation of procollagenase or growth factors indirectly via the formation of plasmin, and in mitogenic activity for osteoblastic cells. Our results suggest that MIF modulates the proliferation of osteoblasts and, moreover, bone tissue remodeling through the PA and plasmin system.
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PMID:Growth factor-induced expression of macrophage migration inhibitory factor in osteoblasts: relevance to the plasminogen activator system. 1063 79

The p27(Kip1) cyclin-dependent kinase inhibitor translocates in response to transforming growth factor-beta to a Cdk2-cyclin E complex inhibiting its catalytic activity, but the p27(Kip1) protein levels are unaffected [1]. We show here that transforming growth factor-beta induces the accumulation of a form of p27(Kip1) representing a subpopulation of total p27(Kip1) in growth-arrested Mv1Lu epithelial cells. The inducible p27(Kip1) is detectable only by a specific p27(Kip1) monoclonal antibody recognizing a native form of p27(Kip1). The increase in this subset of p27(Kip1) correlates with G(1) arrest and withdrawal of the cells from the cycle induced by transforming growth factor-beta, serum starvation, or contact inhibition. In contrast to the majority of p27(Kip1) in the cells, the transforming growth factor-beta-inducible p27(Kip1) is devoid of cyclin-dependent kinase/cyclin interactions. The results indicate that growth arresting treatments induce the accumulation of non-cyclin-dependent kinase-bound p27(Kip1), which may function as a reservoir for inhibition of Cdk2-cyclin E activities.
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PMID:Accumulation of a form of p27(Kip1) not associated with Cdk-cyclin complexes in transforming growth factor-beta-arrested Mv1Lu cells. 1094 83

Because survival and growth of human hepatoma cells are maintained by nutrient, especially glucose, glucose starvation induces acute cell death. The cell death is markedly suppressed by hypoxia, and we have reported involvement of AMP-activated protein kinase-alpha (AMPK-alpha), Akt, and ARK5 in hypoxia-induced tolerance. In the current study we investigated the mechanism of hypoxia-induced tolerance in human hepatoma cell line HepG2. ARK5 expression was induced in HepG2 cells when they were subjected to glucose starvation, and we found that glucose starvation transiently induced Akt and AMPK-alpha phosphorylation and that hypoxia prolonged phosphorylation of both protein kinases. We also found that hypoxia-induced tolerance was partially abrogated by blocking the Akt/ARK5 system or by suppressing AMPK-alpha expression and that suppression of both completely abolished the tolerance, suggesting that AMPK-alpha activation signaling and the Akt/ARK5 system play independent essential roles in hypoxia-induced tolerance. By using chemical compounds that specifically inhibit kinase activity of type I-transforming growth factor-beta (TGF-beta) receptor, we showed an involvement of TGF-beta in hypoxia-induced tolerance. TGF-beta1 mRNA expression was induced by hypoxia in an hypoxia-inducible factor-1alpha-independent manner, and addition of recombinant TGF-beta suppressed cell death during glucose starvation even under normoxic condition. AMPK-alpha, Akt, and ARK5 were activated by TGF-beta1, and Akt and AMPK-alpha phosphorylation, which was prolonged by hypoxia, was suppressed by an inhibitor of type I TGF-beta receptor. Based on these findings, we propose that hypoxia-induced tumor cell tolerance to glucose starvation is caused by hypoxia-induced TGF-beta1 through AMPK-alpha activation and the Akt/ARK5 system.
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PMID:Involvement of transforming growth factor-beta 1 signaling in hypoxia-induced tolerance to glucose starvation. 1601 25

Living organisms represent, in essence, dynamic interactions of high complexity between membrane-separated compartments that cannot exist on their own, but reach behaviour in co-ordination. In multicellular organisms, there must be communication and co-ordination between individual cells and cell groups to achieve appropriate behaviour of the system. Depending on the mode of signal transportation and the target, intercellular communication is neuronal, hormonal, paracrine or juxtacrine. Cell signalling can also be self-targeting or autocrine. Although the notion of paracrine and autocrine signalling was already suggested more than 100 years ago, it is only during the last 30 years that these mechanisms have been characterised. In the anterior pituitary, paracrine communication and autocrine loops that operate during fetal and postnatal development in mammals and lower vertebrates have been shown in all hormonal cell types and in folliculo-stellate cells. More than 100 compounds have been identified that have, or may have, paracrine or autocrine actions. They include the neurotransmitters acetylcholine and gamma-aminobutyric acid, peptides such as vasoactive intestinal peptide, galanin, endothelins, calcitonin, neuromedin B and melanocortins, growth factors of the epidermal growth factor, fibroblast growth factor, nerve growth factor and transforming growth factor-beta families, cytokines, tissue factors such as annexin-1 and follistatin, hormones, nitric oxide, purines, retinoids and fatty acid derivatives. In addition, connective tissue cells, endothelial cells and vascular pericytes may influence paracrinicity by delivering growth factors, cytokines, heparan sulphate proteoglycans and proteases. Basement membranes may influence paracrine signalling through the binding of signalling molecules to heparan sulphate proteoglycans. Paracrine/autocrine actions are highly context-dependent. They are turned on/off when hormonal outputs need to be adapted to changing demands of the organism, such as during reproduction, stress, inflammation, starvation and circadian rhythms. Specificity and selectivity in autocrine/paracrine interactions may rely on microanatomical specialisations, functional compartmentalisation in receptor-ligand distribution and the non-equilibrium dynamics of the receptor-ligand interactions in the loops.
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PMID:Paracrinicity: the story of 30 years of cellular pituitary crosstalk. 1808 53

Cell growth-the primary determinant of cell size-has an intimate relationship with proliferation; cells divide only after they reach a critical size. Despite its developmental and medical significance, little is known about cellular pathways that mediate the growth of cells. Accumulating evidence demonstrates a role for autophagy-a mechanism of eukaryotic cells to digest their own constituents during development or starvation-in cell size control. Increasing autophagic activity by prolonged starvation, rapamycin treatment inhibiting TOR (target of rapamycin) signaling, or genetic intervention, causes cellular atrophy in worms, flies and mammalian cell cultures. In contrast, we have shown that in the nematode Caenorhabditis elegans mutational inactivation of two autophagy genes, unc-51/Atg1 and bec-1/Atg6, confers reduced cell size. We argue that physiological levels of autophagy are required for normal cell size, whereas both insufficient and excessive levels of autophagy lead to retarded cell growth. Furthermore, we discuss data suggesting that the insulin/IGF-1 (insulin-like growth factor receptor-1) and TGF-beta (transforming growth factor-beta) signaling systems acting as major growth regulatory pathways converge on autophagy genes to control cell size. Thus, autophagy may act as a central regulatory mechanism of cell growth.
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PMID:Regulation of cell growth by autophagy. 1825 17

The hepatocyte growth factor (HGF)/Met signaling system is essential for liver development, homeostasis, and function. In this study, we took advantage of a liver-specific, Met-conditional knockout mouse generated in our laboratory to address the molecular mechanisms of HGF/Met signaling in adult liver progenitor cell (oval cell) biology. For this purpose, we isolated oval cells from 3,5-diethoxycarbonyl-1,4-dihydro-collidine-treated Met(flx/flx) mice and established oval cell-derived cell lines that carried either functional (Met(flx/flx)) or a nonfunctional (Met(-/-)) met gene using virus-mediated Cre-loxP recombination. Oval cells lacking Met tyrosine kinase activity displayed neither Met phosphorylation nor activation of downstream targets and were refractory to HGF stimulation. Although Met(-/-) and Met(flx/flx) cells proliferated at similar rates under 10% serum, Met-deficient cells demonstrated decreased cell viability and were more prone to apoptosis when challenged with either serum starvation or the pro-apoptotic cytokine transforming growth factor-beta. Treatment with HGF reduced transforming growth factor-beta-mediated cell death in Met(flx/flx) but not Met(-/-) cells. Importantly, Met(flx/flx) and Met(-/-) cells both constitutively expressed hgf, and conditioned medium from serum-starved oval cells exhibited anti-apoptotic activity in Met(flx/flx) cells. Furthermore, serum-starved Met(flx/flx) cells showed persistent activation of the Met tyrosine kinase, suggesting HGF/Met autocrine regulation. In conclusion, these data reveal a critical, functional role for Met in oval cell survival through an autocrine mechanism.
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PMID:Deletion of the Met tyrosine kinase in liver progenitor oval cells increases sensitivity to apoptosis in vitro. 1838 20


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