Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Telomerase complex maintains the length of the telome, cbre, and protects erosion of the physical ends of the eukaryotic chromosome in all actively dividing cells including cancer cells. Telomerase activation extends the lifespan of cells in culture by maintaining the length of the telomere. Compared to terminally differentiated somatic cells, telomerase activity remains high in over 90% of cancer cells. It has now become clear that the role of telomerase is much more complex than just telomere lengthening. The remaining 10% of cancers deploy ALT (alternative lengthening of telomeres) pathway to maintain telomere length. Telomerase inhibitors offer a good therapeutic option. Also, telomerase-associated molecules can be targeted provided their roles are clearly established. In any case, it is necessary to understand the major role of telomerase in cancer cells. Many studies have already been done to explore gene profiling of a telomerase positive cell by knocking down expression of hTERT (telomerase reverse transcriptase). To complement these studies, we performed global gene profiling of a telomerase negative cell by ectopically expressing hTERT and studied changes in the global gene expression patterns. Analysis of microarray data for telomerase negative cells ectopically expressing telomerase showed 76 differentially regulated genes, out of which 39 genes were upregulated, and 37 were downregulated. Three upregulated genes such as TSPAN13, HMGCS2, DLX5, and three downregulated genes like DHRS2, CRYAB, and PDLIM1 were validated by real-time PCR. Knocking down of TSAPN13 in hTERT overexpressing U2OS cells enhanced the apoptosis of the cells. TSPAN13 knockdown in these cells suppressed mesenchymal properties and enhanced epithelial character.
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PMID:hTERT promotes tumor progression by enhancing TSPAN13 expression in osteosarcoma cells. 2972 72

In this study, the protective effects of a carboxymethyl polysaccharide CMP33 from Poria cocos against inflammatory bowel disease (IBD) were investigated using TNBS-induced colitis in mice. The results showed that CMP33 markedly ameliorated the severity of colitis, including a 2-fold decrease in the mortality rate, a 50% decrease in disease activity index, and a 36%-44% decrease in macro- or microscopic histopathological score, compared with TNBS administration. Moreover, CMP33 decreased the levels of pro-inflammatory cytokines and increased the levels of anti-inflammatory cytokines in the colon tissue and serum of colitic mice. Using iTRAQ-coupled- nano-HPLC-MS/MS-based proteomics, the protein profiles after TNBS, high- or low-dose CMP33 and salazosulfapyridine (SASP) treatments were compared and many differentially expressed proteins were identified. Among them, 7 proteins (Hmgcs2, Fabp2, Hp, B4galnt2, B3gnt6, Sap and Ca1) were proposed to be the common targeting protein group (TPG) of CMP33 and drug SASP. Particularly, some targeting proteins were CMP33-dose-specific: high-dose-specific TPG (Mtco3, Gal-6, Mptx, S100 g and Hpx) and low-dose-specific TPG (Zg16, Hexb, Insl5, Cept1, Hspb6 and Ifi27l2b), suggesting the complex acting mechanism of CMP33. GC-TOF-MS-based metabolomics revealed that oleic acid and dihydrotestosterone could be the common targets of CMP33 and SASP. By integrative analysis of proteomics and metabolomics, key protein-metabolite pathways (PMP) were identified, PMP for high-dose: 2-hydroxybutyric acid - (GPT, GGH) - glutathione - ALB - testosterone - TTR - dihydrotestosterone; PMP for low-dose: (PYY, FABP2, HMGCS2) - oleic acid - TTR - dihydrotestosterone. In total, these results demonstrated the protective effects of CMP33 against IBD in mice through the potential TPG and PMP.
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PMID:The protective effects of Poria cocos-derived polysaccharide CMP33 against IBD in mice and its molecular mechanism. 3037 28