Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51812 (mitogen-activated protein)
 10,636 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cinnamaldehyde (Cin) has been shown to be effective in inducing apoptotic cell death in a number of human cancer cells. The aim of this study was to investigate the effect of pifithrin-alpha (PFTalpha; a specific p53 inhibitor) and mitogen-activated protein kinases (MAPKs) inhibitors [namely SP600125 (a specific JNK inhibitor), SB203580 (a specific p38 inhibitor) and PD98059 (a specific ERK inhibitor)] on apoptotic signaling transduction mechanism induced by Cin in human hepatoma PLC/PRF/5 (CD95-negative) cells. Using XTT assay, Cin exhibited a powerful cytotoxic effect and apoptotic induction in PLC/PRF/5 cells. Apoptosis was elicited when cells were treated with 1 microM Cin as characterized by morphological changes and the appearance of phosphatidylserine on the outer surface of the plasma membrane. Cin down-regulated the expression of Bcl-(XL), up-regulated mutant p53 and Bax proteins and promoted caspase-3 to active forms, as well as cleaving poly (ADP-ribose) polymerase (PARP) in a time-dependent pattern. This could be supported by the activation and phosphorylation of MAPKs, including JNK, ERK and p38 kinases. Pre-incubation with PFTalpha and specific MAPK inhibitors significantly diminished the effect of Cin-induced apoptosis. The activities of anti-apoptotic (Bcl-(XL)) and pro-apoptotic (Bax) proteins were remarkably affected by PFTalpha and PD98059 pre-treatment. PFTalpha effectively blocked PARP cleavage in cells treated with Cin, and also markedly prevented the phosphorylation of JNK, p38 and ERK proteins. These results suggest that p53 induction and MAPK signaling pathways are required for Cin-mediated apoptosis in PLC/PRF/5 cells.
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PMID:MAPK inhibitors and pifithrin-alpha block cinnamaldehyde-induced apoptosis in human PLC/PRF/5 cells. 1767 46

We investigated whether latanoprost has a direct anti-apoptotic effect in retinal ganglion cell (RGC) line and RGCs in the rat. RGC-5 cells were induced to undergo apoptosis by serum deprivation and exogenous glutamate. The level of cell death with or without latanoprost acid was monitored by an XTT assay and by immunocytochemistry with activated caspase-3. Changes in the level of intracellular calcium ([Ca(2+)]i) were measured with fluo-4 fluorescence. The XTT assay revealed that latanoprost acid increased RGC-5 cell viability. Latanoprost acid significantly reduced caspase-3 positive cells and suppressed [Ca(2+)]i evoked by glutamate. U0126, a mitogen-activated protein/extracellular signal-regulated kinase 1 and 2 inhibitor, partially blocked the rescue effect of latnanoprost acid (p=0.013). In vivo, rat RGCs were degenerated by optic nerve crush. After topical instillation of latanoprost for 7days, RGCs labeled with fluorogold were significantly. Retinal flatmounts were subjected to terminal dUTP nick end labeling (TUNEL) staining to detect apoptotic cells. TUNEL-positive cells were significantly decreased in eyes with topically instilled latanoprost (p=0.015). These data suggest that latanoprost has an neuroprotective ability in RGCs.
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PMID:Latanoprost protects rat retinal ganglion cells from apoptosis in vitro and in vivo. 1908 21

p38 mitogen-activated protein kinases (MAPK) are members of the MAPK family that are activated by inflammatory cytokines and a variety of environmental stresses. It mediates various biological processes. p38 MAPK activity play important roles in tumour progression. Excessive p38 expression is observed in invasive breast cancers. The aim of the present study was to investigate whether the p38 siRNA transfection of breast cancer cells is a putative preventive treatment for human breast cancer. p38 siRNA was used at a concentration of 15, 30, and 100 nM in human breast cancer cell lines (MCF-7) and normal fibroblast cell lines (NIH 3T3). After 48 and 72 h of transfection, the reduction in p38 expression was measured using quantitative real-time PCR. The activation of p38 signalling was measured by ELISA. XTT cell proliferation assay was performed to determine the effect of p38 silencing on MCF-7 and NIH 3T3 cell lines. The results demonstrated that approximately 96% gene silencing occurred by the selected siRNA targeting p38 mRNA. The most effective silencing was observed at 72 h post-transfection using 30 nM p38 siRNA. The results of ELISA showed that the expression of p38 protein was inhibited by p38 siRNA at 30 nM siRNA and 100 nM at 72 h post transfection. XTT results showed that cells stimulated by 30 nM siRNA at 72 h post transfection were the lowest in proliferation. p38 siRNA can interfere with the expression of p38 at protein level in MCF-7 cells, result in inhibition of cell proliferation. p38 siRNA may be a critical regulator to promote the proliferation and protein expression in MCF-7 cells. In this study, we demonstrate that p38 silencing is a preventive maintenance for treating breast cancer.
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PMID:The effects of p38 gene silencing on breast cancer cells. 2446 83