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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High-sucrose consumption is associated with increased risk of human colon cancer. Our previous research indicated that high-sucrose diets (vs. cornstarch) promote intestinal epithelial cell proliferation and tumorigenesis as well as increase serum glucose and hepatic IGF-I mRNA levels in APC(Min) mice. To examine the role of functional pathways, in particular of IGF-I signaling, in sucrose-induced intestinal epithelial cell proliferation and tumorigenesis, we examined the effects of dietary carbohydrate source (sucrose vs. cornstarch) on gene expression in the intestinal epithelium using cDNA microarray and quantitative RT-PCR analysis. Dietary carbohydrate source significantly (P < 0.05) altered mRNA expression of 109 known genes in the small intestinal epithelium, including many involved in metabolic pathways. Consumption of high-sucrose diets altered expression levels of genes involved in cell adhesion, cell cycle control, and transduction signaling, consistent with increased risk of intestinal tumorigenesis. High-sucrose intake also affected expression of genes involved in IGF-I signaling, including upregulating IGF-II and downregulating IGFBP3, which supports our hypothesis that IGF-I signaling could play a role in intestinal epithelial cell proliferation and tumorigenesis promoted by high-sucrose consumption.
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PMID:Dietary carbohydrate source alters gene expression profile of intestinal epithelium in mice. 1911 85

Calcium/calmodulin-dependent protein kinase (CaMK) is required for diverse cellular functions, and similar kinases exist in fungi. Although mammalian CaMK kinase (CaMKK) activates CaMK and also evolutionarily-conserved AMP-activated protein kinase (AMPK), CaMKK is yet to be established in yeast. We here report that the fission yeast Schizosaccharomyces pombe Ssp1 kinase, which controls G2/M transition and response to stress, is the putative CaMKK. Ssp1 has a CaM binding domain (CBD) and associates with 14-3-3 proteins as mammalian CaMKK does. Temperature-sensitive ssp1 mutants isolated are defective in the tolerance to limited glucose, and this tolerance requires the conserved stretch present between the kinase domain and CBD. Sds23, multi-copy suppressor for mutants defective in type 1 phosphatase and APC/cyclosome, also suppresses the ssp1 phenotype, and is required for the tolerance to limited glucose. We demonstrate that Sds23 binds to type 2A protein phosphatases (PP2A) and PP2A-related phosphatase Ppe1, and that Sds23 inhibits Ppe1 phosphatase activity. Ssp1 and Ppe1 thus seem to antagonize in utilizing limited glucose. We also show that Ppk9 and Ssp2 are the catalytic subunits of AMPK and AMPK-related kinases, respectively, which bind to common beta-(Amk2) and gamma-(Cbs2) subunits.
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PMID:Schizosaccharomyces pombe cell division cycle under limited glucose requires Ssp1 kinase, the putative CaMKK, and Sds23, a PP2A-related phosphatase inhibitor. 1937 76

Neurons are known to have a lower glycolytic rate than astrocytes and when stressed they are unable to upregulate glycolysis because of low Pfkfb3 (6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase-3) activity. This enzyme generates fructose-2,6-bisphosphate (F2,6P(2)), the most potent activator of 6-phosphofructo-1-kinase (Pfk1; ref. 4), a master regulator of glycolysis. Here, we show that Pfkfb3 is absent from neurons in the brain cortex and that Pfkfb3 in neurons is constantly subject to proteasomal degradation by the action of the E3 ubiquitin ligase, anaphase-promoting complex/cyclosome (APC/C)-Cdh1. By contrast, astrocytes have low APC/C-Cdh1 activity and therefore Pfkfb3 is present in these cells. Upregulation of Pfkfb3 by either inhibition of Cdh1 or overexpression of Pfkfb3 in neurons resulted in the activation of glycolysis. This, however, was accompanied by a marked decrease in the oxidation of glucose through the pentose phosphate pathway (a metabolic route involved in the regeneration of reduced glutathione) resulting in oxidative stress and apoptotic death. Thus, by actively downregulating glycolysis by APC/C-Cdh1, neurons use glucose to maintain their antioxidant status at the expense of its utilization for bioenergetic purposes.
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PMID:The bioenergetic and antioxidant status of neurons is controlled by continuous degradation of a key glycolytic enzyme by APC/C-Cdh1. 1944 25

Extractive microbial transformation of L-phenylacetylcarbinol (L-PAC) in nonionic surfactant Triton X-100 micelle aqueous solution was investigated by response surface methodology. Based on the Box-Behnken design, a mathematical model was developed for the predication of mutual interactions between benzaldehyde, Triton X-100, and glucose on L-PAC production. It indicated that the negative or positive effect of nonionic surfactant strongly depended on the substrate concentration. The model predicted that the optimal concentration of benzaldehyde, Triton X-100, and glucose was 1.2 ml, 15 g, and 2.76 g per 100 ml, respectively. Under the optimal condition, the maximum L-PAC production was 27.6 mM, which was verified by a time course of extractive microbial transformation. A discrete fed-batch process for verification of cell activity was also presented.
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PMID:Investigation of extractive microbial transformation in nonionic surfactant micelle aqueous solution using response surface methodology. 1962 69

Neurons are thought to be particularly vulnerable cells against reactive oxygen and nitrogen species (RONS) damage (nitrosative stress), due in part to their weak antioxidant defense and low ability to compensate energy homeostasis. Intriguingly, nitrosative stress efficiently stimulates the rate of the antioxidant pentose-phosphate pathway (PPP), which generates NADPH a necessary cofactor for the reduction of glutathione disulfide. In fact, inhibition of PPP sensitizes cultured neurons to glutathione oxidation and apoptotic death, whereas its stimulation confers resistance to nitrosative stress. Furthermore, we recently described that neurons can preferentially use glucose through the PPP by inhibiting glycolysis, which is achieved by continuously degrading the glycolytic positive-effector protein, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (Pfkfb3) by the action of the E3 ubiquitine ligase anaphase-promoting complex/cyclosome (APC/C)(Cdh1). These results suggest that the antioxidant fragility of neurons may be compensated by the PPP at the expense of inhibiting bioenergetic glycolysis.
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PMID:The pentose-phosphate pathway in neuronal survival against nitrosative stress. 1993 72

Following inhibition of mitochondrial respiration neurons die rapidly, whereas astrocytes utilize glycolytically-generated ATP to increase their mitochondrial membrane potential, thus becoming more resistant to pro-apoptotic stimuli. Neurons are unable to increase glycolysis due to the lack of activity of the glycolysis-promoting enzyme 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase, isoform 3 (PFKFB3). In neurons, PFKFB3 is degraded constantly via the E3 ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C)- CDH1. Glucose metabolism in neurons is directed mainly to the pentose phosphate pathway, leading to regeneration of reduced glutathione. In addition to their relevance to brain physiology and pathophysiology, these observations suggest that APC/C-CDH1 might link activation of glycolysis and cell proliferation as it is also involved in the regulation of cell cycle proteins.
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PMID:Glycolysis: a bioenergetic or a survival pathway? 2000 13

Neurons preconditioned with non-injurious hypoxia or the anesthetic isoflurane express different genes but are equally protected against severe hypoxia/ischemia. We hypothesized that neuroprotection would be augmented when preconditioning with isoflurane and hypoxic preconditioning are combined. We also tested if preconditioning requires intracellular Ca(2+) and the inositol triphosphate receptor, and if gene expression is similar in single agent and combined preconditioning. Hippocampal slice cultures prepared from 9 day old rats were preconditioned with hypoxia (95% N(2), 5% CO(2) for 15 min, HPC), 1% isoflurane for 15 min (APC) or their combination (CPC) for 15 min. A day later cultures were deprived of O(2) and glucose (OGD) to produce neuronal injury. Cell death was assessed 48 h after OGD. mRNA encoding 119 signal transduction genes was quantified with cDNA micro arrays. Intracellular Ca(2+) in CA1 region was measured with fura-2 during preconditioning. The cell-permeable Ca(2+) buffer BAPTA-AM, the IP(3) receptor antagonist Xestospongin C and RNA silencing were used to investigate preconditioning mechanisms. CPC decreased CA1, CA3 and dentate region death by 64-86% following OGD, more than HPC or APC alone (P<0.01). Gene expression following CPC was an amalgam of gene expression in HPC and APC, with simultaneous increases in growth/development and survival/apoptosis regulation genes. Intracellular Ca(2+) chelation and RNA silencing of IP(3) receptors prevented preconditioning neuroprotection and gene responses. We conclude that combined isoflurane-hypoxia preconditioning augments neuroprotection compared to single agents in immature rat hippocampal slice cultures. The mechanism involves genes for growth, development, apoptosis regulation and cell survival as well as IP(3) receptors and intracellular Ca(2+).
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PMID:Enhanced hypoxic preconditioning by isoflurane: signaling gene expression and requirement of intracellular Ca2+ and inositol triphosphate receptors. 2043 34

Colorectal carcinoma is among the most common malignancies. The tumour cells may arise from mutations in genes encoding proteins involved in the regulation of cell survival and proliferation. Recent evidence disclosed the sensitivity of colon carcinoma to the expression of ubiquitous serum and glucocorticoid inducible kinase-1 (SGK1). The kinase is activated by insulin and growth factors via the phosphatidylinositide-3-kinase (PI3K) and the 3-phosphoinositide dependent kinase (PDK1). SGK1 regulates channels, carriers and Na(+)/K(+)-ATPase, enzymes such as glycogen-synthase-kinase-3 (GSK3) and ubiquitin-ligase Nedd4-2, as well as several transcription factors. SGK1 regulates transport, hormone release, neuroexcitability, inflammation, cell proliferation and apoptosis. SGK1 contributes to metabolic syndrome and the pathophysiology of neurodegeneration, allergy, peptic ulcer, fibrosing disease and response to ischemia. SGK1 is upregulated in some tumours but downregulated in others. SGK1-sensitive mechanisms fostering tumour growth include activation of K(+) channels and Ca(2+) channels, Na(+)/H(+) exchanger, amino acid transporters and glucose transporters, upregulation of the nuclear factor NFkappaB and beta-catenin as well as downregulation of the transcription factors Foxo3a/FKHRL1 and p53. SGK1 enhances survival, invasiveness, motility, epithelial to mesenchymal transition and adhesiveness of tumour cells. Following deficiency of APC (adenoma polyposis coli) or chemical cancerogenesis, SGK1 knockout mice develop less intestinal tumours than their wild-type littermates and pharmacological SGK1 inhibition counteracts growth of prostate cancer cells.
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PMID:Colorectal carcinoma cells--regulation of survival and growth by SGK1. 2054 Oct 34

Cell proliferation is accompanied by an increase in the utilization of glucose and glutamine. The proliferative response is dependent on a decrease in the activity of the ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C)-Cdh1 which controls G1-to-S-phase transition by targeting degradation motifs, notably the KEN box. This occurs not only in cell cycle proteins but also in the glycolysis-promoting enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3 (PFKFB3), as we have recently demonstrated in cells in culture. We now show that APC/C-Cdh1 controls the proliferative response of human T lymphocytes. Moreover, we have found that glutaminase 1 is a substrate for this ubiquitin ligase and appears at the same time as PFKFB3 in proliferating T lymphocytes. Glutaminase 1 is the first enzyme in glutaminolysis, which converts glutamine to lactate, yielding intermediates for cell proliferation. Thus APC/C-Cdh1 is responsible for the provision not only of glucose but also of glutamine and, as such, accounts for the critical step that links the cell cycle with the metabolic substrates essential for its progression.
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PMID:Anaphase-promoting complex/cyclosome-Cdh1 coordinates glycolysis and glutaminolysis with transition to S phase in human T lymphocytes. 2104 50

The rRNA and ribosome biogenesis (RRB) regulon from Saccharomyces cerevisiae contains some 200 genes, the expression of which is tightly regulated under changing cellular conditions. RRB gene promoters are enriched for the RRPE and PAC consensus motifs, and a significant fraction of RRB genes are found as adjacent gene pairs. A genetic analysis of the MPP10 promoter revealed that both the RRPE and PAC motifs are important for coordinated expression of MPP10 following heat shock, osmotic stress, and glucose replenishment. The association of the RRPE binding factor Stb3 with the MPP10 promoter was found to increase after glucose replenishment and to decrease following heat shock. Similarly, bulk histone H3 clearing and histone H4K12 acetylation levels at the MPP10 promoter were found to increase or decrease following glucose replenishment or heat shock, respectively. Interestingly, substitutions in the PAC and RRPE sequences at the MPP10 promoter were also found to impact the regulated expression of the adjacent RRB gene YJR003, whose promoter lies in the opposite orientation and some 3.8 kb away. Furthermore, the regulated expression of YJR003C could be disrupted by inserting a reporter cassette that increased its distance from MPP10. Given that a high incidence of gene pairing was also found within the ribosomal protein (RP) and RRB regulons across different yeast species, our results indicate that immediately adjacent positioning of genes can be functionally significant for their coregulated expression.
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PMID:Adjacent gene pairing plays a role in the coordinated expression of ribosome biogenesis genes MPP10 and YJR003C in Saccharomyces cerevisiae. 2111 40


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