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)

During sclerotial infection of Sclerotinia sclerotiorum the mycoparasite Coniothyrium minitans penetrates through the host cell wall, which contains beta-1,3-glucan as its major component. A PCR-based strategy was used to clone a beta-1,3-glucanase-encoding gene, designated cmg1, from a cDNA library of the fungus. The nucleotide and deduced amino acid sequences of this gene showed high levels of similarity to the sequences of other fungal exo-beta-1,3-glucanase genes. The calculated molecular mass of the deduced protein (without the predicted 24-amino-acid N-terminal secretion signal peptide) was 83,346 Da, and the estimated pI was 4.73. Saccharomyces cerevisiae INVSc1 expressing the cmg1 gene secreted a approximately 100-kDa beta-1,3-glucanase enzyme (as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis) into the culture medium. N-terminal sequence analysis of the purified recombinant enzyme revealed that the secreted enzyme starts at Ala-32, seven amino acids downstream from the predicted signal peptidase cleavage site. The purified recombinant glucanase inhibited in vitro mycelial growth of S. sclerotiorum by 35 and 85% at concentrations of 300 and 600 microg x ml(-1), respectively. A single copy of the cmg1 gene is present in the genome of C. minitans. Northern analyses indicated increases in the transcript levels of cmg1 due to both carbon starvation and the presence of ground sclerotia of S. sclerotiorum; only slight repression was observed in the presence of 2% glucose. Expression of cmg1 increased during parasitic interaction with S. sclerotiorum.
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PMID:Expression of cmg1, an exo-beta-1,3-glucanase gene from Coniothyrium minitans, increases during sclerotial parasitism. 1115 56

Choline is an essential nutrient for cell survival and proliferation, however, the expression and function of choline transporters have not been well identified in cancer. In this study, we detected the mRNA and protein expression of organic cation transporter OCT3, carnitine/cation transporters OCTN1 and OCTN2, and choline transporter-like protein CTL1 in human lung adenocarcinoma cell lines A549, H1299 and SPC-A-1. Their expression pattern was further confirmed in 25 human primary adenocarcinoma tissues. The choline uptake in these cell lines was significantly blocked by CTL1 inhibitor, but only partially inhibited by OCT or OCTN inhibitors. The efficacy of these inhibitors on cell proliferation is closely correlated with their abilities to block choline transport. Under the native expression of these transporters, the total choline uptake was notably blocked by specific PI3K/AKT inhibitors. These results describe the expression of choline transporters and their relevant function in cell proliferation of human lung adenocarcinoma, thus providing a potential choline-starvation strategy of cancer interference through targeting choline transporters, especially CTL1.
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PMID:Choline transporters in human lung adenocarcinoma: expression and functional implications. 1780 61

The responses of insect cells to starvation and the characteristics of cell death after the depletion of nutrients remain largely unknown. In the present study, we investigated autophagy, apoptosis and necrosis in two Lepidoptera insect cell lines in response to amino acid starvation. Our data demonstrated that starvation induced a significant increase in autophagy in Spodoptera litura SL-ZSU-1 cells, and cell apoptosis followed autophagy after starvation of more than 48h. However, at an early stage of starvation, inhibition of autophagy with 3-MA rapidly triggered apoptosis of SL-ZSU-1 cells, suggesting autophagy inhibits cell apoptosis. By contrast, Bombyx mori SPC Bm36 cells died by a non-apoptotic pathway if the starvation was prolonged for more than 48 h. At the early stage of starvation, inhibition of autophagy with 3-MA did not trigger apoptosis in Bm36 cells, but resulted in necrotic-like cell death. Under starvation pressure, autophagy in SL-ZSU-1 cells was much more active than in Bm36 cells. The activity of caspase-9-like in apoptotic SL-ZSU-1 cells also was much higher than in apoptotic Bm36 cells. RT-PCR analyses revealed that transcriptional levels of saposin-like (Bm109) and Atg6 were undetectable in Bm36 cells, but expression level of saposin-like in SL-ZSU-1 was high. Expression of Atg6 in SL-ZSU-1 cells was not analyzed because its sequence was unknown. These data indicate that autophagy prevents Lepidoptera insect cells from death at an early stage of starvation, but prolonged starvation results in cell death. The pathways of cell death might be dependent on the abundance of caspase-9-like, saposin-like and Atg6.
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PMID:Responses of two insect cell lines to starvation: autophagy prevents them from undergoing apoptosis and necrosis, respectively. 2133 11

Proteins secreted by bacteria perform functions vital for cell survival and play a role in virulence in Mycobacterium tuberculosis. M. tuberculosis lepB (Rv2903c) encodes the sole homolog of the type I signal peptidase (SPase). The lepB gene is essential in M. tuberculosis, since we could delete the chromosomal copy only when a second functional copy was provided elsewhere. By placing expression under the control of an anhydrotetracycline-inducible promoter, we confirmed that reduced lepB expression was detrimental to growth. Furthermore, we demonstrated that a serine-lysine catalytic dyad, characteristic for SPase function, is required for LepB function. We confirmed the involvement of LepB in the secretion of a reporter protein fused to an M. tuberculosis signal peptide. An inhibitor of LepB (MD3; a beta-aminoketone) was active against M. tuberculosis, exhibiting growth inhibition and bactericidal activity. Overexpression of lepB reduced the susceptibility of M. tuberculosis to MD3, and downregulation resulted in increased susceptibility, suggesting that LepB is the true target of MD3. MD3 lead to a rapid loss of viability and cell lysis. Interestingly, the compound had increased potency in nonreplicating cells, causing a reduction in viable cell numbers below the detection limit after 24 h. These data suggest that protein secretion is required to maintain viability under starvation conditions and that secreted proteins play a critical role in generating and surviving the persistent state. We conclude that LepB is a promising novel target for drug discovery in M. tuberculosis, since its inhibition results in rapid killing of persistent and replicating organisms.
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PMID:Inhibition of the sole type I signal peptidase of Mycobacterium tuberculosis is bactericidal under replicating and nonreplicating conditions. 2242 25