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)

To date, the acquired immunodeficiency syndrome (AIDS) has been identified in over 50 children in the US, including those with associated hemophilia, high-risk environmental factors (Haitian background, parental intravenous drug abuse, or prostitution), and blood transfusions. The evaluation of an infant or young child in whom AIDS is suspected requires exclusion of congenital disorders of immune function. A specific test is not currently available, but inclusion criteria for childhood AIDS have been developed. The diseases accepted as indicative of underlying cellular immunodeficiency children are the same as those used in defining AIDS in adults, with the exclusion of congenital infections such as toxoplasmosis or herpes simplex virus infection in the 1st month of life or cytomegalovirus infection in the 1st 6 months of life. Specific conditions that must be excluded in children are primary immunodeficiency diseases (e.g., DiGeorge syndrome, Wiskott-Aldrich syndrome, ataxia-telangiectasia, neutrophil function abnormality) and secondary immuno-deficiency associated with immunosuppressive therapy, lymphoreticular malignancy, or starvation. Almost all young children with AIDS have hepatosplenomegaly, interstitial pneumonitis, and poor growth. The average age of 36 US child AIDS victims studied in detail was 5 months at presentation with findings suggestive of severe immunodeficiency. Mucocutaneous candidiasis was present in 75% of these 36 children, and Pneumocystis carinii and cytomegalovirus were each isolated from 30% of cases. Normal T4:T8 ratios occur in about 15% of pediatric AIDS cases. Laboratory evidence of polyclonal hypergammaglobulinemia generally supports the AIDS diagnosis. Recurrent infection and malnutrition are major problems in the clinical management of child AIDS patients.
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PMID:Acquired immune deficiency syndrome in childhood. 298 8

The nucleotide sequence of the yeast gene TRP5 and its 5' and 3' flanking regions was determined. The deduced coding sequence for tryptophan synthase contains 2,127 base pairs. The protein chain has a calculated molecular weight of 76,544. Yeast tryptophan synthase, a bifunctional protein, has a primary structure which corresponds to an Escherichia coli tryptophan synthase alpha chain-beta chain fusion. An NH2-terminal 239 amino acid segment of yeast tryptophan synthase is homologous with E. coli tryptophan synthase alpha subunit, while a distal 389 amino acid residue segment is homologous to the E. coli tryptophan synthase beta chain. This order of segments of the yeast enzyme is the reverse of the chromosomal order characteristic of all prokaryotes that have been examined. The two segments are joined by a connecting region of 28 residues in the yeast enzyme which is not homologous to either the alpha or beta chains of the bacterial enzyme. A portion of the connecting region of yeast tryptophan synthase exhibits nucleotide sequence similarity to the 3' terminus of E. coli trpC and the trpC-trpB intercistronic region. Active site cysteine, histidine, and lysine residues in the beta 2 subunit of E. coli tryptophan synthase are conserved in the yeast enzyme. Also conserved in the yeast enzyme are 6/8 amino acid residues having an important role in maintaining the structure and function of the E. coli tryptophan synthase alpha subunit. S1 nuclease mapping was used to identify three major mRNA transcripts with different 5' termini. Potential T-A-T-A sites for transcription initiation were identified, as well as other sequences that occur frequently in yeast genes. A 5' flanking region of TRP5 was shown by DNA/DNA hybridization to be present in multiple copies in the yeast genome. TRP5 mRNA levels, measured by RNA/DNA hybridization, increased 2- to 7-fold in response to starvation for either tryptophan or histidine, indicating transcriptional regulation.
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PMID:Yeast gene TRP5: structure, function, regulation. 627 87

The effect of sucrose feeding on endogenous intestinal RNA polymerase activities and on chromatin structure was studied in rats. Adult rats were given a 70% sucrose solution for 15 hours following a 48-hour starvation period. Comparison was made with rats starved for 63 hours and with ad libitum nourished animals. Chromatin-bound RNA polymerase I activity was significantly reduced by starvation. Sucrose feeding provoked a significant rise in the activity, but the level found in the nourished rats was not reached. The free poly[d(A-T)]-dependent RNA polymerase I activity of the sucrose-fed rats exceeded that of the starved and the nourished animals. Chromatin-bound RNA polymerase II activity was enhanced most markedly by sucrose feeding. The balance between the chromatin-bound and free enzymes was shifted towards the chromatin-bound state when compared to the starved and nourished rats. Starvation caused a reduction in the size of oligonucleosomes but sucrose feeding restored almost entirely the original pattern obtained in the nourished animals. These results reflect modifications in the structure of chromatin after sucrose feeding. The present report demonstrates that the adaptive processes triggered in the intestine by dietary sucrose are associated with changes in gene expression.
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PMID:Modulation of RNA polymerase activities in the intestine of adult rats by dietary sucrose. 661 82

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

Although ATM, the protein defective in ataxia-telangiectasia (A-T), is activated primarily by radiation, there is also evidence that expression of the protein can be regulated by both radiation and growth factors. Computer analysis of the ATM promoter proximal 700-bp sequence reveals a number of potentially important cis-regulatory sequences. Using nucleotide substitutions to delete putative functional elements in the promoter of ATM, we examined the importance of some of these sites for both the basal and the radiation-induced activity of the promoter. In lymphoblastoid cells, most of the mutations in transcription factor consensus sequences [Sp1(1), Sp1(2), Cre, Ets, Xre, gammaIre(2), a modified AP1 site (Fse), and GCF] reduced basal activity to various extents, whereas others [gammaIre(1), NF1, Myb] left basal activity unaffected. In human skin fibroblasts, results were generally the same, but the basal activity varied up to 8-fold in these and other cell lines. Radiation activated the promoter approximately 2.5-fold in serum-starved lymphoblastoid cells, reaching a maximum by 3 hr, and all mutated elements equally blocked this activation. Reduction in Sp1 and AP1 DNA binding activity by serum starvation was rapidly reversed by exposure of cells to radiation. This reduction was not evident in A-T cells, and the response to radiation was less marked. Data provided for interaction between ATM and Sp1 by protein binding and co-immunoprecipitation could explain the altered regulation of Sp1 in A-T cells. The data described here provide additional evidence that basal and radiation-induced regulation of the ATM promoter is under multifactorial control.
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PMID:Site-directed mutagenesis of the ATM promoter: consequences for response to proliferation and ionizing radiation. 1293 43

Ataxia telangiectasia (A-T) is an autosomal, recessive disorder mainly characterized by neuronal degeneration. However, the reason for neuronal degeneration in A-T patients is still unclear. ATM (A-T, mutated), the gene mutated in A-T, encodes a 370-kDa protein kinase. We measured the levels of the ATM protein found in differentiated neuron-like rat PC12 cells and differentiated neuron-like human SH-SY5Y cells. We found that, in rat PC12 cells, ATM levels decreased dramatically after differentiation, which is consistent with previous results observed in differentiated mouse neural progenitor cells. In contrast, the levels of ATM were similar before and after differentiation in human SH-SY5Y cells. Using an indirect immunofluorescence assay, we showed that ATM translocates from the nucleus to the cytoplasm in differentiated human SH-SY5Y cells. The translocation of ATM was further verified by subcellular fractionation experiments. The constitutive expression and cytoplasmic translocation of ATM in differentiated SH-SY5Y cells suggest that ATM is important for maintaining the regular function of human neuronal cells. Our results further demonstrated that, in response to insulin, ATM protects differentiated neuron-like SH-SY5Y cells from serum starvation-induced apoptosis. These data provide the first evidence that cytoplasmic ATM promotes survival of human neuronal cells in an insulin-dependent manner.
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PMID:Constitutive expression and cytoplasmic compartmentalization of ATM protein in differentiated human neuron-like SH-SY5Y cells. 1724 Nov 56

Aberrant activation of Akt plays a pivotal role in cancer development. ATM, a protein deficient in patients with ataxia-telangiectasia disease, is traditionally considered as a nuclear protein kinase that functions as a signal transducer in response to DNA damage. It has recently been shown that ATM is also a cytoplasmic protein that mediates the full activation of Akt in response to insulin. Our study shows that a specific ATM inhibitor, KU-55933, blocks the phosphorylation of Akt induced by insulin and insulin-like growth factor I in cancer cells that exhibit abnormal Akt activity. Moreover, KU-55933 inhibits cancer cell proliferation by inducing G(1) cell cycle arrest. It does so through the downregulation of the synthesis of cyclin D1, a protein known to be elevated in a variety of tumors. In addition, KU-55933 treatment during serum starvation triggers apoptosis in these cancer cells. Our results suggest that KU-55933 may be a novel chemotherapeutic agent targeting cancer resistant to traditional chemotherapy or immunotherapy due to aberrant activation of Akt. Furthermore, KU-55933 completely abrogates rapamycin-induced feedback activation of Akt. Combination of KU-55933 and rapamycin not only induces apoptosis, which is not seen in cancer cells treated only with rapamycin, but also shows better efficacy in inhibiting cancer cell proliferation than each drug alone. Therefore, combining KU-55933 with rapamycin may provide a highly effective approach for improving mammalian target of rapamycin-targeted anticancer therapy that is currently hindered by rapamycin-induced feedback activation of Akt.
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PMID:The ATM inhibitor KU-55933 suppresses cell proliferation and induces apoptosis by blocking Akt in cancer cells with overactivated Akt. 2005 81

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder characterized by cerebellar ataxia and oculocutaneous telangiectasias. The gene mutated in this disease, ATM (A-T, mutated), encodes a 370-kDa Ser/Thr protein kinase. ATM not only mediates cellular response to DNA damage but also acts as an activator of Akt in response to insulin. However, despite intensive studies, the mechanism underlying the neuronal degeneration symptoms of human A-T is still poorly understood. We found that the topoisomerase inhibitors etoposide and camptothecin readily induced apoptosis in undifferentiated proliferating SH-SY5Y cells but could not induce apoptosis in neuronally differentiated SH-SY5Y cells. In addition, etoposide induced p53 phosphorylation and H2AX foci formation in proliferating SH-SY5Y cells but failed to do so in differentiated SH-SY5Y cells. Moreover, while inhibition of ATM in undifferentiated SH-SY5Y cells partially protected them from etoposide-induced apoptosis, the same treatment had no effect on cell viability in differentiated SH-SY5Y cells. These results suggest that DNA damage or defective response to DNA damage is not the cause of neuronal cell death in human A-T. In contrast, we discovered that Akt phosphorylation was inhibited when ATM activity was suppressed in differentiated SH-SY5Y cells. Furthermore, inhibition of ATM induced apoptosis following serum starvation in neuronally differentiated SH-SY5Y cells but could not trigger apoptosis under the same conditions in undifferentiated proliferating SH-SY5Y cells. These results demonstrate that ATM mediates the Akt signaling and promotes cell survival in neuron-like human SH-SY5Y cells, suggesting that impaired activation of Akt is the reason for neuronal degeneration in human A-T.
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PMID:Functional switching of ATM: sensor of DNA damage in proliferating cells and mediator of Akt survival signal in post-mitotic human neuron-like cells. 2273 65

Mitochondria supply cellular energy and also perform a role in the adaptation to metabolic stress. In mammals, the ataxia-telangiectasia mutated (ATM) kinase acts as a redox sensor controlling mitochondrial function. Subsequently, transcriptomic and genetic studies were utilized to elucidate the role played by a fungal ATM homolog during carbon starvation. In Aspergillus nidulans, AtmA was shown to control mitochondrial function and glucose uptake. Carbon starvation responses that are regulated by target of rapamycin (TOR) were shown to be AtmA-dependent, including autophagy and hydrolytic enzyme secretion. AtmA also regulated a p53-like transcription factor, XprG, inhibiting starvation-induced XprG-dependent protease secretion and cell death. Thus, AtmA possibly represents a direct or indirect link between mitochondrial stress, metabolism, and growth through the influence of TOR and XprG function. The coordination of cell growth and division with nutrient availability is crucial for all microorganisms to successfully proliferate in a heterogeneous environment. Mitochondria supply cellular energy but also perform a role in the adaptation to metabolic stress and the cross-talk between prosurvival and prodeath pathways. The present study of Aspergillus nidulans demonstrated that AtmA also controlled mitochondrial mass, function, and oxidative phosphorylation, which directly or indirectly influenced glucose uptake. Carbon starvation responses, including autophagy, shifting metabolism to the glyoxylate cycle, and the secretion of carbon scavenging enzymes were AtmA-dependent. Transcriptomic profiling of the carbon starvation response demonstrated how TOR signaling and the retrograde response, which signals mitochondrial dysfunction, were directly or indirectly influenced by AtmA. The AtmA kinase was also shown to influence a p53-like transcription factor, inhibiting starvation-induced XprG-dependent protease secretion and cell death. Therefore, in response to metabolic stress, AtmA appears to perform a role in the regulation of TOR signaling, involving the retrograde and SnfA pathways. Thus, AtmA may represent a link between mitochondrial function and cell cycle or growth, possibly through the influence of the TOR and XprG function.
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PMID:The Aspergillus nidulans ATM kinase regulates mitochondrial function, glucose uptake and the carbon starvation response. 2419 33

Phosphorus (P) is an essential macronutrient for crop development and production. Phosphate starvation response 1 (PHR1) acts as the central regulator for Pi-signaling and Pi-homeostasis in plants by binding to the cis-element PHR1 binding sequence (P1BS; GNATATNC). However, how phosphate starvation-induced gene expression is regulated remains obscure. In this work, we investigated the DNA binding affinity of the PHR1 ortholog OsPHR2 to its downstream target genes in Oryza sativa (rice). We confirmed that a combination of P1BS and P1BS-like motifs are essential for stable binding by OsPHR2. Furthermore, we report that variations in P1BS motif bases affected the binding affinity of OsPHR2 and that the highest affinity motif was GaATATtC (designated the A-T-type P1BS). We also found that a combination of two A-T-type P1BS elements in tandem, namely HA-P1BS, was very efficient for binding of OsPHR2. Using the cis-regulator HA-P1BS, we modified the promoters of Transporter Traffic Facilitator 1 (PHF1), a key factor controlling endoplasmic reticulum-exit of phosphate transporters to the plasma membrane, for efficient uptake of phosphorous in an energetically neutral way. Transgenic plants with the modified promoters showed significantly enhanced tolerance to low phosphate stress in both solution and soil conditions, which provides a new strategy for crop improvement to enhance tolerance of nutrient deficiency.
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PMID:Genetic manipulation of a high-affinity PHR1 target cis-element to improve phosphorous uptake in Oryza sativa L. 2565 19


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