Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.61 (caspase-8)
 6,833 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxidative stress is one of the major causes of neuronal cell death in disorders such as perinatal hypoxia and ischemia. Protein phosphorylation is the most significant PTM of proteins and plays an important role in stress-induced signal transduction. Thus, the analysis of alternative protein phosphorylation states which occur during oxidative stress-induced cell death could provide valuable information regarding cell death. In this study, a reference phosphoproteome map of the mouse hippocampal cell line HT22 was constructed based on 125 spots that were identified by MALDI-TOF or LC-ESI-Q-TOF-MS analysis. In addition, proteins of HT22 cells at various stages of oxidative stress-induced cell death were separated by 2-DE and alterations in phosphoproteins were detected by Pro-Q Diamond staining. A total of 17 spots showing significant quantitative changes and seven newly appearing spots were identified after glutamate treatment. Splicing factor 2, peroxiredoxin 2, S100 calcium binding protein A11, and purine nucleoside phosphorylase were identified as up- or down-regulated proteins. CDC25A, caspase-8, and cyp51 protein appeared during oxidative stress-induced cell death. The data in this study from phosphoproteomic analysis provide a valuable resource for the understanding of HT22 cell death mechanisms mediated by oxidative stress.
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PMID:Phosphoproteomic analysis of neuronal cell death by glutamate-induced oxidative stress. 1761 Feb 4

A new diterpene, identified as (+)-6-(4-hydroxy-4-methyl-2-pentenoyl)-4,6-dimethyl-5-(3-methyl-2-butenyl)-1,3-cyclohexadienecarbaldehyde (1, cubelin), was isolated from a methanol extract of Litsea cubeba fruits by normal phase column chromatography and purified by preparative HPLC. The structure elucidation was conducted by spectroscopic methods (UV, IR, ESI-TOF-MS, 1-D and 2-D NMR). Cubelin exhibited activity against HeLa cell viability and proliferation. The cells also exhibited changes in nuclear morphology which are hallmarks of apoptotic cell death. The presence of cleaved caspase-3/-7, caspase-8 and caspase-9 in the cubelin treated population indicated the potential of the compound to induce apoptosis in HeLa cells via both intrinsic and extrinsic pathways.
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PMID:A new diterpene from Litsea cubeba fruits: structure elucidation and capability to induce apoptosis in HeLa cells. 2485 70

The main purpose of this study was to investigate the active components of the Chinese medicine formula Shenqi San (SS) by high performance liquid chromatography with diode array detector and electrospray ionization-hybrid quadrupole time-of-flight mass spectrum (HPLC-DADESI- QTOF-MS), and demonstrate the anticancer mechanism of SS on human lung adenocarcinoma A549 cells by evaluating the cell proliferation and apoptosis induction. The chloroform extraction of SS (CE-SS) was extracted from SS, while HPLC-DAD-ESI-QTOF-MS assay was performed to identify components of CE-SS. MTT assay was used to quantify the proliferation of A549 cells with the treatment of CE-SS. Apoptosis analysis was carried out by detecting phosphatidylserine (PS) externalization using the Annexin V-FITC Apoptosis Detection Kit and the stained cells were analyzed with a flow cytometer. DAPI staining assay was carried out to observe morphological characteristics of apoptotic cells. Western blotting was used to detect the expression of important signaling proteins including caspase-3, -8, -9, p53, Bax and Bcl-2. Eight compounds were identified through HPLC-DAD-ESI-QTOF-MS analysis and 3-pyridine carboxylic acid, barbatin C, scutebarbatine F and barbatine D might be the main compounds responsible for the antitumor effect of CE-SS. CE-SS suppressed the proliferation of lung cancer A549 cells in a time- and dose-dependent manner. By Annexin V-FITC/PI double staining, we found that treatment with CE-SS induced apoptosis in A549 cells. After 24-h exposure to CE-SS, the expression of cleaved-caspase-9, cleaved-caspase-8 and cleaved-caspase-3 protein was activated, the expression of p53 protein increased while the ratio of Bax/Bcl-2 also increased. This study identified the eight compounds of CE-SS, and demonstrated their anticancer effect on human lung adenocarcinoma A549 cells via induction of apoptosis.
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PMID:Chinese medicine formula "Shenqi San" extract inhibits proliferation of human lung adenocarcinoma A549 cells via inducing apoptosis. 2927 Jul 64