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)

Tartrate-resistant acid phosphatase (TRAP) is highly expressed in osteoclasts and chondroclasts. The present study investigated changes in TRAP activity after chondrocyte death and cartilage damage, and also evaluated the possible use of TRAP as a diagnostic factor in a model of osteoarthritis. We induced experimental osteoarthritis in beagle dogs and separated chondrocytes from articular cartilage using an enzyme probe. Chondrocyte death was induced by proteasome inhibition and TRAIL treatment, and levels of lactate dehydrogenase, reactive oxygen species (ROS), caspase activation and TRAP activity were measured in the chondrocytes and synovial fluid. Proteasome inhibition and TRAIL treatment significantly enhanced chondrocyte death via caspase-8 activation and ROS generation in the primary cultured canine chondrocytes. TRAP activity was highly increased in damaged chondrocytes, but was decreased by blocking chondrocyte death using caspase inhibition or an ROS scavenger. In the synovial fluid of osteoarthritic dogs, TRAP activity as well as caspase activation and ROS levels were higher than those in the normal joint. Our study demonstrated that TRAP is activated by apoptosis and oxidative stress in primary cultured chondrocytes and osteoarthritic joints and also suggests that TRAP may be used as a diagnostic biomarker for detection of cartilage-related diseases, including osteoarthritis.
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PMID:Tartrate-resistant acid phosphatase as a diagnostic factor for arthritis. 1951 35

Nerve growth factor (NGF) is known to regulate both cancer cell survival and death signaling, depending on the cellular circumstances, in various cell types. In this study, we showed that NGF strongly upregulated the protein level of tropomyosin-related kinase A (TrkA) in TrkA-inducible SK-N-MC cancer cells, resulting in increases in various TrkA-dependent cellular processes, including the phosphorylation of c-Jun N-terminal kinase (JNK) and caspase-8 cleavage. In addition, NGF enhanced TrkA-induced morphological changes and cell death, and this effect was significantly suppressed by the JNK inhibitor SP600125, but not by the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin. To investigate novel targets associated with the enhancement of TrkA-induced SK-N-MC cell death caused by NGF, we performed Coomassie Brilliant Blue staining and two-dimensional (2D) proteomic analysis in TrkA-inducible SK-N-MC cells. We identified 31 protein spots that were either greatly upregulated or downregulated by TrkA during NGF treatment using matrix-associated laser desorption/ionization time of flight/time of flight mass spectrometry, and we analyzed the effects of SP600125 and wortmannin on the spots. Interestingly, 11 protein spots, including heterogeneous nuclear ribonucleoprotein K (hnRNP K), lamin B1 and TAR DNA-binding protein (TDP43), were significantly influenced by SP600125, but not by wortmannin. Moreover, the NGF/TrkA-dependent inhibition of cell viability was significantly enhanced by knockdown of hnRNP K using small interfering RNA, demonstrating that hnRNP K is a novel target associated with the regulation of TrkA-dependent SK-N-MC cancer cell death enhanced by NGF.
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PMID:Proteomic analysis of novel targets associated with the enhancement of TrkA-induced SK-N-MC cancer cell death caused by NGF. 2722 80