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)

Thrombopoietin (TPO) has been demonstrated to have proliferative effects on hematopoietic progenitor cells and maturational effects on more committed populations which express a megakaryocyte lineage-specific phenotype. M07e is a GM-CSF or interleukin 3 (IL-3)-dependent human leukemic cell line having surface markers characteristic of both myeloid progenitors and megakaryocytes. The effects of TPO on the proliferation and survival of M07e cells were investigated. Following an 18-h factor starvation period to remove residual growth factor signals and phase the cells in G0/G1, TPO provides a weak proliferative signal to M07e compared to IL-3 or GM-CSF treatment under the same conditions. However, TPO synergizes with both GM-CSF and IL-3, and to a greater extent with steel factor, a competence factor for M07e, in the induction of cellular proliferation. TPO sustains cellular integrity of M07e during prolonged (18 days) growth factor withdrawal and also protects M07e cells in serum-free conditions. In addition, preincubation of M07e for 72 h in TPO maintains its survival for subsequent cytokine-induced proliferation, while control media do not. TPO suppresses growth factor withdrawal-induced apoptosis as evaluated by flow cytometric detection of both in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling and cellular DNA content via propidium iodide staining. These results suggest a role for TPO as a survival factor for M07e cells.
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PMID:Thrombopoietin suppresses apoptosis and behaves as a survival factor for the human growth factor-dependent cell line, M07e. 872 99

The phenomenon of starvation-induced apoptosis was studied in cultures of a mouse B lymphocyte hybridoma. In a continuous culture the limitation of nutrients was modelled by dilution of a protein-free medium with saline to 15%. Surprisingly, the hybridoma clone did not die out under extreme starvation conditions. A steady state was established in which the cells continued to grow at very low viable cell concentration, concomitantly with an enhanced rate of apoptotic death. Suppression of the death rate, and increase of steady-state viable cell concentration, could be achieved by additions of L-alanine, L-asparagine or L-glutamine, but not by addition of L-phenylalanine. This specificity pattern is in agreement with previous screening experiments that have identified a set of apoptosis-preventing amino acids (glycine, L-alanine, L-serine, L-threonine, L-proline, L-asparagine, L-glutamine, L-histidine). The analysis of amino acid consumption and production showed a consistent production of alanine and serine both in standard medium and in diluted media. When alanine was added at a final concentration of 2 mM to media diluted either to 40 or 20%, apoptosis was partly suppressed. A limited production of alanine was observed also in alanine-enriched diluted media. It is concluded that the apoptosis-preventing amino acids act as signal molecules, besides their nutritive function, and that the signal has a character of a survival factor. The observed phenomena are interpreted in terms of a survival-control mechanism that regulates the viable cell number of a lymphocyte clone in an adequate proportion with the level of available nutrients.
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PMID:Protection of B lymphocyte hybridoma against starvation-induced apoptosis: survival-signal role of some amino acids. 890 9

Endothelin-1 (ET-1), an endothelium-derived vasoactive peptide, functions as a potent vasoconstrictor as well as mitogen. We show here a novel role for ET-1 as an apoptosis survival factor for cultured rat endothelial cells. When we rendered endothelial cells obtained from rat aorta quiescent by serum starvation, significant portions of cultured cells underwent apoptotic death as demonstrated by nucleosomal laddering on agarose gel electrophoresis, flow cytometry analysis with FACS, and the TdT-mediated dUTP biotin nick-end labeling (TUNEL) method. ET-1 dose-dependently (10[-12] to 10[-6] mol/L) suppressed the apoptosis induced by serum starvation. The ET(B) receptor antagonist (BQ788; 10[-6] mol/L) and ET(A/B) receptor antagonists (PD142893 and PD145065; 10[-6] mol/L), but not the ET(A) receptor antagonist (BQ123; 10[-6] mol/L), blocked the apoptosis protective effect of 10[-7] mol/L ET-1. Nonimmune rabbit serum reduced the apoptotic event induced by serum deprivation, whereas neutralization of endogenous ET-1 by polyclonal anti-ET-1 antiserum abrogated this protective effect. The ET(B) receptor antagonist (BQ788; 10[-8] to 10[-6] mol/L), but not the ET(A) receptor antagonist (BQ123; 10[-8] to 10[-6] mol/L), significantly inhibited proliferation of endothelial cells. These data suggest that ET-1, as well as mitogen, functions as an apoptosis survival factor for endothelial cells in an autocrine/paracrine manner via the ET(B) receptor.
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PMID:Endothelin-1 as an autocrine/paracrine apoptosis survival factor for endothelial cells. 936 76

Adrenomedullin is a novel vasodilatory peptide originally isolated from pheochromocytoma. Recently, we found that adrenomedullin acts as an autocrine/paracrine apoptosis survival factor for rat endothelial cells. In the present study, we show that adrenomedullin induces the expression of Max, a heterodimeric partner of c-Myc, which may contribute to its ability to rescue endothelial cells from apoptosis. Max is a basic-helix-loop-helix-leucine zipper protein that forms heterodimers with its alternative partners, Mad and Mxi-1, to behave as an antagonist for Myc-Max heterodimer through competition for common DNA targets. The expression of Max is reported to be constitutive and more stable than c-Myc, and serum induces immediate c-Myc stimulation followed by modest Max up-regulation. In quiescent rat endothelial cells, adrenomedullin stimulated the expression of Max without affecting c-Myc. Quantitation with real-time quantitative PCR detected on the ABI Prism 7700 Sequence Detection System revealed that adrenomedullin and calcitonin gene-related peptide (CGRP), as well as serum, up-regulated Max mRNA levels and that down-regulation of Max mRNA after serum deprivation was prevented by adrenomedullin. Neither adrenomedullin nor CGRP affected c-Myc expression. Transfection of a Max-expressing plasmid into endothelial cells rescued the apoptosis induced by serum deprivation. Neutralization with anti-adrenomedullin antiserum or blockade with a CGRP receptor antagonist, CGRP(8-37), reduced Max mRNA levels in growing endothelial cells and enhanced apoptosis after serum starvation. Introduction of an antisense oligodeoxynucleotide against Max mRNA using transferrin receptor-operated transfer led to inhibition of both adrenomedullin-induced up-regulation of Max transcripts and its cell survival effect, whereas random, sense, or missense oligonucleotides were without effect. The negative regulation of E-box-driven transcription by adrenomedullin was demonstrated by using preproendothelin-1 promoter containing c-Myc-Max binding consensus sequence; the promoter activity of preproendothelin-1 was reduced by cotransfecting Max- and Mad-expressing plasmids as well as addition of adrenomedullin and CGRP. The present results demonstrate that adrenomedullin antagonizes serum deprivation-induced endothelial apoptosis by up-regulation of the max gene in an autocrine/ paracrine manner.
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PMID:Induction of max by adrenomedullin and calcitonin gene-related peptide antagonizes endothelial apoptosis. 1044 8

Leptin mediates neuroendocrine responses to fasting and restores the starvation-induced changes of several hypothalamic neuropeptides. Ciliary neurotrophic factor (CNTF), a cytokine closely related to leptin, reduces food intake and reverses obesity, but its role in restoring the starvation-induced changes of hormones or hypothalamic neuropeptides remains largely unknown. To comparatively assess the roles of CNTF and leptin in reversing the starvation-induced changes of hypothalamic neuropeptides and endocrine function and in inducing expression of hypothalamic inhibitors of leptin and CNTF signaling (suppressor of cytokine signaling 3 [SOCS-3]) and mediators of energy expenditure (cyclo-oxygenase 2 [COX-2]), we studied the effect of CNTF and leptin administered by intraperitoneal injections (1 microg/g twice daily) in C57Bl/6J mice fasted for 48 h. Serum corticosterone levels increased with fasting, and leptin administration partially normalized them, whereas CNTF administration had no effect. Hypothalamic neuropeptide Y (NPY) and agouti-related protein (AgRP) mRNA expression increased and pro-opiomelanocortin (POMC) decreased in response to fasting. Leptin administration decreased NPY and AgRP and increased POMC mRNA levels toward baseline, but CNTF administration in fasted mice had no effect of comparable significance. Both leptin and CNTF administration in fasted mice resulted in an induction of SOCS-3 mRNA expression. CNTF also induced hypothalamic SOCS-2 mRNA expression. Finally, neither leptin nor CNTF administration in mice fasted for 48 h alters hypothalamic COX-2 expression. Our data suggest that only falling leptin levels mediate the starvation-induced alterations in corticosterone levels and expression of hypothalamic neuropeptides, but inhibitors of leptin signaling are induced by both leptin and CNTF. This may be of clinical importance because both agents are now being evaluated for the treatment of obesity in humans.
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PMID:Unlike leptin, ciliary neurotrophic factor does not reverse the starvation-induced changes of serum corticosterone and hypothalamic neuropeptide levels but induces expression of hypothalamic inhibitors of leptin signaling. 1107 56

Multiple myeloma (MM) is a plasma-cell disorder in which malignant plasma cells accumulate in the bone marrow and usually produce a monoclonal immunoglobulin. Usual presenting features of overt MM include recurrent osteolytic lesions, bacterial infections, anemia and renal insufficiency. MM is responsible for about 1 percent of all cancer-related deaths in Western countries. Its epidemiologic pattern remains obscure, and its cause unknown [1]. The presence of somatic mutations within the immunoglobulin genes of myeloma cells indicate that the putative myeloma-cell precursors have been stimulated by antigens within germinal centers and are either memory B cells or migrating plasmablasts. Myeloma cells proliferate slowly in the bone marrow and display a weak apoptotic index in vivo [2]. This suggest that some defects in the apoptotic process could be involved in this neoplasia. Interleukin-6 (IL-6) is known to be an essential survival factor of myeloma cells and to protect them from apoptosis induced by different stimuli (e.g. dexamethasone, CD95, serum starvation, gamma-irradiation). More recently, important works have been devoted to the biology of the soluble form of the IL-6R alpha i.e., sIL-6R alpha. These works give IL-6/sIL-6R alpha complex an important role in the biology of IL-6. The purpose of the current review is to emphasize the role of this complex in the pathogenesis of MM.
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PMID:The role of interleukin-6 and interleukin-6/interleukin-6 receptor-alpha complex in the pathogenesis of multiple myeloma. 1112 96

Several chemokines, belonging to both the CXC and CC classes, act as positive or negative regulators of angiogenesis. We sought to investigate the role of CXCL13, B cell-attracting chemokine 1 (BCA-1), also known as B-lymphocyte chemoattractant (BLC), on endothelial cell functions. We tested the effect of CXCL13 on HUVEC chemotaxis and proliferation in the presence of fibroblast growth factor (FGF)-2 and found that such chemokine inhibits FGF-2-induced functions, while is not active by itself. To test whether other FGF-2-mediated biological activities may be affected, we evaluated the ability of CXCL13 to rescue HUVEC from starvation-induced apoptosis, as FGF-2 is a survival factor for endothelial cells, and found that CXCL13 partially inhibits such rescue. Multiple mechanisms may be responsible for these biological activities as CXCL13 displaces FGF-2 binding to endothelial cells, inhibits FGF-2 homodimerization, and induces the formation of CXCL13-FGF-2 heterodimers. Our data suggest that CXCL13 may modulate angiogenesis by interfering with FGF-2 activity.
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PMID:The chemokine CXCL13 (BCA-1) inhibits FGF-2 effects on endothelial cells. 1170 70

Leptin is a 16 kDa protein mainly produced by adipose tissue in proportion to adipose tissue mass. Originally thought to be a satiety factor, leptin is a pleiotropic molecule. In addition to playing a role in energy regulation, leptin also regulates endocrine and immune functions. Both the structure of leptin and that of its receptor suggest that leptin might be classified as a cytokine. The secondary structure of leptin has similarities to the long-chain helical cytokines family, which includes interleukin 6 (IL-6), IL-11, CNTF, and LIF, and the leptin receptor is homologous to the gp-130 signal-transducing subunit of the IL-6-type cytokine receptors. Leptin plays a role in innate and acquired immunity. Leptin levels increase acutely during infection and inflammation, and may represent a protective component of the host response to inflammation. More important, leptin deficiency increases susceptibility to infectious and inflammatory stimuli and is associated with dysregulation of cytokine production. Leptin deficiency also causes a defect in hematopoiesis. Leptin regulates T cells responses, polarizing Th cells toward a Th1 phenotype. Low leptin levels occurring during starvation mediate the neuroendocrine and immune dysfunction of starvation.
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PMID:Leptin regulation of the immune response and the immunodeficiency of malnutrition. 1172 31

We identified a novel human AMP-activated protein kinase (AMPK) family member, designated ARK5, encoding 661 amino acids with an estimated molecular mass of 74 kDa. The putative amino acid sequence reveals 47, 45.8, 42.4, and 55% homology to AMPK-alpha1, AMPK-alpha2, MELK, and SNARK, respectively, suggesting that it is a new member of the AMPK family. It has a putative Akt phosphorylation motif at amino acids 595-600, and Ser(600) was found to be phosphorylated by active Akt resulting in the activation of kinase activity toward the SAMS peptide, a consensus AMPK substrate. During nutrient starvation, ARK5 supported the survival of cells in an Akt-dependent manner. In addition, we also demonstrated that ARK5, when activated by Akt, phosphorylated the ATM protein that is mutated in the human genetic disorder ataxia-telangiectasia and also induced the phosphorylation of p53. On the basis of our current findings, we propose that a novel AMPK family member, ARK5, is the tumor cell survival factor activated by Akt and acts as an ATM kinase under the conditions of nutrient starvation.
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PMID:Identification of a novel protein kinase mediating Akt survival signaling to the ATM protein. 1240 6

Interleukin-6 (IL-6) is a major survival factor for malignant plasma cells involved in multiple myeloma. Using an RNase protection assay, we looked for gene expression of 10 anti- and proapoptotic Bcl-2-family proteins in 12 IL-6-dependent human myeloma cell lines (HMCL). A high Mcl-1 gene expression was found in all HMCLs and the other genes were variably expressed. Out of the 10 Bcl-2-family members, only the Mcl-1 gene was regulated by IL-6. Upon starvation of IL-6, Mcl-1 gene expression decreased in association with myeloma cell apoptosis and was upregulated after adding IL-6 again in association with myeloma cell survival. A constitutive Mcl-1 expression was induced with an Mcl-1-GFP retrovirus in two IL-6-dependent HMCLs. The Mcl-1 HMCLs have a marked reduced apoptosis upon IL-6 starvation compared to HMCLs transduced with control GFP retrovirus and may grow without adding IL-6. These data emphasize the major role of Mcl-1 antiapoptotic protein in the IL-6-induced survival of human myeloma cells.
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PMID:A major role for Mcl-1 antiapoptotic protein in the IL-6-induced survival of human myeloma cells. 1277 46


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