Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.24 (mitogen-activated protein kinase)
 95,810 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amyloidbetapeptide (A beta) is implicated in neuronal cell death in Alzheimer's disease, but the molecular mechanisms are still unclear. We analyzed its mechanism and found several potential rescue factors against A beta-mediated apoptosis. A beta(1-40) stimulated phosphorylation of tau and JNK and induced cell death in SH-SY5Y cells. The cell death was inhibited by insulin-like growth factor-1, suggesting that the JNK pathway may be involved in A beta(1-40)-induced cytotoxicity. Using the human fetus brain cDNA library-targeted differential display technique, a new gene BF5-1 (32aa) was found as a rescue factor against A beta(1-40). BF5-1 has partially the same amino acid sequences as those of the C-terminus of cytochrome c oxidase subunit VIIb (COX-VIIb). COX-VIIb mRNA is increased in AD brains and its overexpression in cells enhanced A beta(1-40)-toxicity. These data suggest that BF5-1 may act as a dominant negative mutant of COX-VIIb. A beta(1-42) also induced cell death in rat neuroblastoma B104 cells, which was abolished by addition of IL-11. By cDNA subtraction analysis in the cell death, the enhanced expression of L-phosphoserine phosphatase was found, but this was also abolished by IL-11. The glutamate neurotoxicity was stimulated in the presence of D-serine, suggesting that NMDA receptors may be involved in A beta(1-42)-induced cytotoxicity. A beta(1-42) also induced increase of a new gene p18A beta rP (p18-amyloid-beta-responsive protein; 166 aa) mRNA expression; overexpression of this gene in PC12 cells induced cell death. By the application of a death trap method, a new gene, p60TRP (p60-Transcription-Regulating-Protein; rat:539 aa, human:547aa), was found as a potential rescue factor against the cell death by p18A beta rP. Thus, our cell death systems and/or new rescue proteins may provide suitable tools for the establishment of drug screening systems leading to the identification of new low-molecular candidates applicable for the treatment of AD.
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PMID:[Possible mechanisms of A beta(1-40)- or A beta(1-42)-induced cell death and their rescue factors]. 1533 86

Growing evidence indicates that phosphoserine phosphatase (PSPH) is up-regulated and correlates with prognosis in multiple types of cancer. However, little is known about the roles of PSPH in NSCLC. Thus, the aim of the present study was to demonstrate the expression of PSPH in human NSCLC and reveal its biological functions and the underlying mechanisms. qRT-PCR, western blot and immunohistochemistry were used to assess the expression of NSCLC patient specimens and NSCLC cell lines. The functions of PSPH in migration and invasion were determined using trans-well and wound-healing assays. Cell proliferation capacity was performed by cell counting kit-8 (CCK-8), colony formation assays and cell cycle analysis. We demonstrated that PSPH was overexpressed in NSCLC specimens compared with the adjacent non-tumorous specimens, and high expression of PSPH was associated with clinical stage, metastasis and gender in NSCLC. Decreased expression of PSPH inhibited NSCLC cells migration, invasion and proliferation. Most importantly, further experiments demonstrated that PSPH might regulate NSCLC progress through MAPK signaling pathways. Lastly, immunohistochemistry (IHC) revealed that the PSPH expression level was positively correlated with the clinical stage in NSCLC patients. These results suggest that PSPH may act as a putative oncogene and a potential therapeutic target in NSCLC.
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PMID:PSPH Mediates the Metastasis and Proliferation of Non-small Cell Lung Cancer through MAPK Signaling Pathways. 3066 58