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)

Muscle damage with a lack of regeneration, manifests itself in several life-threatening diseases, including cancer cachexia, congestive heart failure, AIDS and sepsis. Often misdiagnosed as a condition simply of weight loss, cachexia is actually a highly complex metabolic disorder involving features of anorexia, anaemia, lipolysis and insulin resistance. A significant loss of lean body mass arises from such conditions, resulting in wasting of skeletal muscle. Unlike starvation, the weight loss seen in chronic illnesses arises equally from loss of muscle and of fat. The cachectic state is particularly problematic in cancer, typifying poor prognosis and often lowering responses to chemotherapy and radiation treatment. More than half of cancer patients suffer from cachexia, and strikingly, nearly one-third of cancer deaths are related to cachexia rather than the tumour burden. In considering this disorder, we are faced with a conundrum; how is it possible for uncontrolled growth to prevail in the tumour, in the face of unrestrained tissue loss in our muscles? Consistently, the catabolic state has been associated with a shift in the homeostatic balance between muscle synthesis and degradation mediated by the actions of growth factors and cytokines. Indeed, tumour necrosis factor-alpha (TNF-alpha) levels are raised in several animal models of cachectic muscle wasting, whereas the insulin-like growth factor (IGF) system acts potently to regulate muscle development, hypertrophy and maintenance. This concept of skeletal muscle homeostasis, often viewed as the net balance between two separate processes of protein synthesis and degradation has however changed. More recently, the view is that these two biochemical processes are not occurring independently of each other but in fact are finely co-ordinated by a web of intricate signalling networks. This review, therefore, aims to discuss data currently available regarding the mechanisms of degeneration and regeneration with specific emphasis on the potential and controversial cross-talk which may exist between anabolic growth factors (e.g. IGF-I) and catabolic cytokines (e.g. TNF-alpha). Also importantly, the potential impact at a cellular level of exercise, diet and age will be addressed. Finally, the ability to 'hi-jack' signalling pathways traditionally believed to be for growth and survival or death will be reviewed. It is anticipated that such a review will highlight significant gaps in our knowledge of the cachectic state as well as provide caution with regards to therapeutics suggesting total block on inflammatory processes such as that associated with TNF-alpha action.
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PMID:Waste management - cytokines, growth factors and cachexia. 1711 96

The cDNA and genomic DNA of zebrafish (Danio rerio) protein kinase Cmu (PKCmu), with its promoter region, were obtained. The 508-amino acid zebrafish PKCmu has 86.17% similarity to human PKCmu. Real-time reverse-transcription polymerase chain reaction analysis with starvation and hormonal treatment found significant differences between the control group and the experimental group after 14 days of starvation. After injecting insulin-like growth factor II (IGF-II), growth hormone (GH), insulin, or human chorionic gonadotropin, significant differences were observed between the control and experimental groups 24 h after treatment. After injecting the gonadotropin-releasing hormone or luteotropin-releasing hormone, significant differences were seen between the control and experimental groups 15 h after treatment. These results suggest that in vivo PKCmu expression is regulated by the insulin family or by the GH, but other sex hormones produced a significant expression level more quickly than the insulin family and GH. The zebrafish PKCmu gene is located on zebrafish chromosome 17 and consists of 16 exons. A 2.6 kilobase pair on the 5' flanking region displayed maximal promoter activity in the zebrafish liver (ZFL) cell line after treatment with IGF-I, IGF-II, and GH. However, a 1.6 kilobase pair on the 5' flanking region displayed maximal promoter activity in the HeLa cell line after treatment with IGF-I, IGF-II, and GH. Finally, PKCmu may have important nuclear effects on cell growth and may involve nuclear localization. By transiently transfecting ZFL cells with various zebrafish PKCmu segments, we identified a nuclear localization signal: the amino acid sequence between amino acids 206 and 209 was able to predominantly direct enhanced green fluorescence protein (EGFP) into the nucleus, whereas a deletion of this motif abrogated the nuclear localization property.
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PMID:Cloning and expression analysis of a protein kinase C gene, PKCmu, and its regulation of the promoter region in zebrafish. 1757 Jul 65

The effects of photoperiod and feeding regimes on plasma IGF-I levels and their relationship with growth rate of juvenile halibut (initial mean weight 364 g) were investigated by rearing fish under five different photoperiod regimes and two feeding regimes for 14 months. The entire photoperiod experiment was divided into 3 phases where the fish in each phase were exposed to either natural photoperiod (N), stimulated photoperiod with long day and short night (S) or continuous light (L). Thus, the following five photoperiod combinations were tested: a) Control group (NNN) b) Group 2A (NLN) c) Group 2B (NNL) d) Long day-natural group (SNN) e) Production group (LNN). In addition, the Control group was split into two parts and fed according to two different feeding regimes: a) Continuous fed group: Fish fed every day. b) Starvation/re-fed group: Fish were starved for 5 weeks and then re-fed for 10 weeks, and the treatment repeated during the whole experimental period. The analyses of IGF-I were performed from individually tagged fish in all groups in September 2005 and March 2006. In order to test how rapidly starvation affects circulating IGF-I levels samples were taken from the Starvation/re-fed group after a 10 days starvation (September) and immediately after 10 weeks of feeding (March). A significant relationship between IGF-I levels and individual growth in the preceding period and photoperiod and starvation treatment was found on both occasions. In conclusion, the present study indicates that plasma IGF-I levels are correlated to growth in Atlantic halibut, and affected by photoperiod treatment or compensatory growth during re-feeding. Correlation between individual growth rate and IGF-I levels was low, but significant, highlighting the complexity of how environmental factors affect the endocrine and physiological regulation of growth in fish.
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PMID:Plasma insulin-like growth factor-I concentrations and growth in juvenile halibut (Hippoglossus hippoglossus): effects of photoperiods and feeding regimes. 1857 60

Our studies in yeast have shown that the down-regulation of major signal transduction mediators increases stress resistance and causes an up to 10 fold chronological life span extension. Whereas other laboratories have proposed that sirtuins (Sir2 and its homologs), a family of conserved proteins which are NAD(+)-dependent histone deacetylases, can extend longevity in various model organisms, we propose that one sirtuin, i.e., Sir2, can also accelerate cellular aging and death. In Saccharomyces cerevisiae (yeast), the deletion of Sir2 increases DNA damage but in combination with longevity mutations in principal intracellular signal transduction mediators, or in combination with calorie restriction it causes a further increase in the chronological lifespan as well as an increase in the stress resistance and a major reduction in age-dependent genomic instability. Our recent results also provide evidence for a role of the mammalian Sir2 ortholog SirT1 in the activation of a highly conserved neuronal pathway and in the sensitization of neurons to oxidative damage. However, the mean lifespan of the SirT1(+/-) mice is not different from that of wild type animals, and the survival of SirT1(-/-) mice was reduced under both normal and calorie restricted conditions. Here, I review the studies linking SirT1, IGF-I signaling and starvation in various model organisms with a focus on the post-mitotic cells, which indicate that sirtuins can play both protective and pro-aging roles.
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PMID:Linking sirtuins, IGF-I signaling, and starvation. 1863 38

Beta-hydroxy-beta-methylbutyrate (HMB), a leucine catabolite, has been shown to prevent exercise-induced protein degradation and muscle damage. We hypothesized that HMB would directly regulate muscle-cell proliferation and differentiation and would attenuate apoptosis, the latter presumably underlying satellite-cell depletion during muscle degradation or atrophy. Adding various concentrations of HMB to serum-starved myoblasts induced cell proliferation and MyoD expression as well as the phosphorylation of MAPK/ERK. HMB induced differentiation-specific markers, increased IGF-I mRNA levels and accelerated cell fusion. Its inhibition of serum-starvation- or staurosporine-induced apoptosis was reflected by less apoptotic cells, reduced BAX expression and increased levels of Bcl-2 and Bcl-X. Annexin V staining and flow cytometry analysis showed reduced staurosporine-induced apoptosis in human myoblasts in response to HMB. HMB enhanced the association of the p85 subunit of PI3K with tyrosine-phosphorylated proteins. HMB elevated Akt phosphorylation on Thr308 and Ser473 and this was inhibited by Wortmannin, suggesting that HMB acts via Class I PI3K. Blocking of the PI3K/Akt pathway with specific inhibitors revealed its requirement in mediating the promotive effects of HMB on muscle cell differentiation and fusion. These direct effects of HMB on myoblast differentiation and survival resembling those of IGF-I, at least in culture, suggest its positive influence in preventing muscle wasting.
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PMID:Beta-hydroxy-beta-methylbutyrate (HMB) stimulates myogenic cell proliferation, differentiation and survival via the MAPK/ERK and PI3K/Akt pathways. 1921 Oct 28

Starvation exerts critical influence on somatotroph and leptin secretion. Fasting enhances GH levels in normal subjects, but not in GH hyposecretory states, while it always inhibits leptin secretion. We aimed to clarify the GH/IGF-I and metabolic response to short-term fasting in a GH hypersecretory state such as acromegaly. To this goal, in 8 active acromegalic (ACRO) and in 7 normal women (NS) we evaluated mean GH (mGHc), leptin (mLEPc), insulin (mINSc), glucose (mGLUc) concentrations as well as IGF-I, IGF binding protein (IGFBP)-3, IGFBP-1, and free fatty acid (FFA) levels before and after 36-h fasting. Before fasting, mGHc, IGF-I, mINSc, mGLUc, and FFA levels in ACRO were higher (p<0.01) than in NS. IGFBP-3, IGFBP-1, and mLEPc were similar in ACRO and in NS. Fasting clearly (p<0.02) increased mGHc in NS only. After 36-h fasting, significant IGF-I reduction was recorded in NS only (p<0.03). IGFBP-3 did not change both in ACRO and NS. IGFBP-1 significantly increased (p<0.05) after fasting in both groups but in ACRO were lower (p<0.03) than in NS. Fasting decreased (p<0.03) mLEPc, mGLUc, and mINSc in ACRO as well as in NS; mINSc and mGLUc after fasting in ACRO persisted higher (p<0.005) than in NS. FFA levels were increased by fasting in NS (p<0.02), but not in ACRO. This study shows that GH/IGF-I axis, glucose metabolism, and lypolisis but not leptin display some degree of refractoriness to short-term fasting in acromegaly. The lack of any GH response to fasting in acromegaly would likely reflect neuroendocrine alterations secondary to the GH hypersecretory state. On the other hand, the lack of somatotropic response and the peculiarly blunted metabolic reaction to short-term fasting would partially reflect the delayed adaptation of insulin resistance to starvation.
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PMID:Growth hormone/insulin-like growth factor I axis, glucose metabolism, and lypolisis but not leptin show some degree of refractoriness to short-term fasting in acromegaly. 1924 78

Activation of tumor-stromal interactions is considered to play a critical role in the promotion of tumorigenesis. To discover new therapeutic targets for hormone-refractory prostate tumor growth under androgen ablation therapy, androgen-sensitive LNCaP cells and the derived sublines, E9 (androgen-low-sensitive), and AIDL (androgen-insensitive), were recombined with androgen-dependent embryonic rat urogenital sinus mesenchyme (UGM). Tumors of E9 + UGM and AIDL + UGM were approximately three times as large as those of LNCaP + UGM. Tumors grown in castrated hosts exhibited reduced growth as compared with those in intact hosts. However, in castrated hosts, E9 + UGM and AIDL + UGM tumors were still approximately twice as large as those of LNCaP + UGM. Cell proliferation in tumors of E9 + UGM and AIDL + UGM grown in castrated host, was significantly higher than that in tumors of LNCaP + UGM. In vitro, expression of fibroblast growth factor (FGF)-2 and IGF-I, but not FGF-7 mRNA, was significantly reduced in UGM under androgen starvation. In cell culture, E9 cells were responsive to FGF-2 and FGF-7 stimulation, while AIDL responded to FGF-7 and IGF-1. Expression of FGFR1 and FGFR2 was considerably higher in E9 than those in LNCaP, similarly expression of FGFR2 and IGF-IR were elevated in AIDL. These data suggest that activation of prostate cancer cell growth through growth factor receptor expression may result in the activity of otherwise androgen-independent stromal growth factor signals such as FGF-7 under conditions of androgen ablation.
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PMID:Evidence that androgen-independent stromal growth factor signals promote androgen-insensitive prostate cancer cell growth in vivo. 1929 88

Insulin-like growth factor-binding proteins (IGFBPs) play a vital role in regulating the biological activities of IGFs. In this study, we cloned and determined full-length cDNA sequences of yellowtail IGFBP-1, -2, -3 and -5. Their tissue distribution was determined by real-time quantitative RT-PCR, which revealed that IGFBP-1, -2, -3 and -5 are widely distributed in yellowtail tissues. In yellowtail, both IGFBP-1 and -2 are highly expressed in the liver, IGFBP-3 is predominantly expressed in the heart and skin, with the lowest expression in the liver, and IGFBP-5 is highly expressed in the liver and kidneys. The widespread tissue expression of the yellowtail IGFBPs suggests that they may act in an autocrine and/or paracrine manner in the regulation of IGF activity. The effects of nutritional deprivation on yellowtail IGFBPs and IGF-I were also examined. During a 15-day starvation period, significant elevation was observed in hepatic yellowtail IGFBP-1. Refeeding restored its level to that of the control. No significant change was observed in the hepatic yellowtail IGFBP-2 mRNA levels in starved fish compared with control fish during the starvation period. Interestingly, during the early period of food deprivation, a significant increase was observed in hepatic yellowtail IGFBP-3 and -5 mRNA levels, concomitant to the significant elevation in hepatic IGF-I mRNA from day 3 to day 9. The unexpected increase in growth stimulatory IGFBPs and IGF-I during nutritional deprivation may represent a species-specific response to changes in nutritional condition.
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PMID:Molecular characterization, tissue distribution patterns and nutritional regulation of IGFBP-1, -2, -3 and -5 in yellowtail, Seriola quinqueradiata. 1952 84

Medulloblastoma is the most frequent type of childhood brain tumour. The insulin-like growth factor I receptor (IGF-IR) plays a significant neuroprotective role in medulloblastoma survival through regulation of the downstream effectors of the phosphoinositide-3-kinase-protein kinase-B (PI3K-PKB/c-Akt) pathway. One such target is Forkhead box O1 (FOXO1; FKHR), which is part of the FOXO family of Forkhead transcription factors. Phosphorylation by Akt results in cytoplasmic sequestration of FOXO1 thus inhibiting the expression of genes controlling cell death, cell proliferation, differentiation, cellular metabolism and oxidative stress. Here we show that serum starvation of medulloblastoma cells is accompanied by nuclear translocation of FOXO1. IGF-I stimulation of serum-starved cells resulted in rapid phosphorylation of Akt and FOXO1, and was associated with a significant increase in cell viability. In contrast, expression of a constitutively active form of FOXO1 that cannot be phosphorylated led to a significant reduction in medulloblastoma cell viability, even in the presence of growth factors provided by fetal bovine serum (FBS). These data suggest that the transcription factor FOXO1 may be a critical effector of medulloblastoma growth suppression.
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PMID:Impaired medulloblastoma cell survival following activation of the FOXO1 transcription factor. 1978 58

The effects of short-time fasting on appetite, growth, and nutrient were studied in Atlantic salmon (Salmo salar) smolts. Feed deprivation did change the energy metabolism with reduced plasma protein and muscle indispensible amino acid levels. Plasma levels of ghrelin were significantly higher in starved salmon compared with fed fish after 2 days, but no differences in circulating ghrelin were found between treatments after 14 days. Two mRNA sequences for ghrelin-1 and ghrelin-2, 430 and 533 bp long, respectively, were detected. In addition, the growth hormone secretagogues-receptor like receptor (GHSR-LR) 1a and 1b were identified. Ghrelin-1 but not ghrelin-2 mRNA levels were affected by starvation in the stomach. Lower ghrelin-1 mRNA levels were detected at day 2 in starved fish compared with fed fish. The mRNA levels of GHSR-LR1a were not affected by starvation. Fasting reduced the phenotypic growth and the transcription of insulin-like growth factor (IGF)-II together with IGF-IIR, but IGF-I mRNA were not regulated in fasted salmon after 14 days. Three IGF-binding proteins (IGFBP) at 23, 32, and 43 kDa were found in salmon, and circulating 23 kDa was significantly increased after 14 days of starvation compared with fed fish, indicating increased catabolism. The levels of IGFBP-1 mRNA were significantly higher in fed and starved fish after 14 days compared to those at the start of the experiment, but no significant difference was observed between the treatments. In conclusion, we have shown that circulating ghrelin and ghrelin-1 mRNA is related to changes in energy metabolism in Atlantic salmon.
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PMID:Effects of short-term starvation on ghrelin, GH-IGF system, and IGF-binding proteins in Atlantic salmon. 2087 68


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