Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P05412 (c-Jun)
 11,453 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dissociated cerebellar granule cells maintained in medium containing 25 mM potassium undergo an apoptotic death when switched to medium with 5 mM potassium. Granule cells from mice in which Bax, a proapoptotic Bcl-2 family member, had been deleted, did not undergo apoptosis in 5 mM potassium, yet did undergo an excitotoxic cell death in response to stimulation with 30 or 100 microM NMDA. Within 2 h after switching to 5 mM K+, both wild-type and Bax-deficient granule cells decreased glucose uptake to <20% of control. Protein synthesis also decreased rapidly in both wild-type and Bax-deficient granule cells to 50% of control within 12 h after switching to 5 mM potassium. Both wild-type and Bax -/- neurons increased mRNA levels of c-jun, and caspase 3 (CPP32) and increased phosphorylation of the transactivation domain of c-Jun after K+ deprivation. Wild-type granule cells in 5 mM K+ increased cleavage of DEVD-aminomethylcoumarin (DEVD-AMC), a fluorogenic substrate for caspases 2, 3, and 7; in contrast, Bax-deficient granule cells did not cleave DEVD-AMC. These results place BAX downstream of metabolic changes, changes in mRNA levels, and increased phosphorylation of c-Jun, yet upstream of the activation of caspases and indicate that BAX is required for apoptotic, but not excitotoxic, cell death. In wild-type cells, Boc-Asp-FMK and ZVAD-FMK, general inhibitors of caspases, blocked cleavage of DEVD-AMC and blocked the increase in TdT-mediated dUTP nick end labeling (TUNEL) positivity. However, these inhibitors had only a marginal effect on preventing cell death, suggesting a caspase-independent death pathway downstream of BAX in cerebellar granule cells.
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PMID:Bax deletion further orders the cell death pathway in cerebellar granule cells and suggests a caspase-independent pathway to cell death. 931 40

The toxicity of thapsigargin, a selective inhibitor of endoplasmic reticular Ca2+-ATPase, was investigated in osteoblasts. We induced apoptosis in murine osteoblastic MC3T3E1 cells by exposure to the thapsigargin. Thapsigargin transiently increased the phosphotransferase activity of c-Jun N-terminal kinases1 (JNK1), which might in turn activate transcriptional activity of activation protein-1 (AP-1). We then prepared extracts from thapsigargin-treated MC3T3E1 cells and monitored cleavage of acetyl-YVAD-AMC and acetyl-DEVD-AMC, fluorogenic substrates for caspase 1-like and caspase 3-like proteases, respectively. Thapsigargin significantly increased the proteolytic activity of caspase 3-like proteases, but not the activity of caspase 1-like proteases. Furthermore, thapsigargin increased the transcriptional activity of nuclear factor-kappaB (NF-kappaB). These data suggest that thapsigargin-induced apoptosis in osteoblasts may be via activation of JNK1, caspase 3-like family proteases, and transcriptional factors including AP-1 and NF-kappaB.
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PMID:Signal transduction of thapsigargin-induced apoptosis in osteoblast. 1051 Nov 12

Trichosanthin (TCS) is a type I ribosome--inactivating protein, which inhibits cell viability in human epithelial type 2 (HEp-2) and AMC-HN-8 human laryngeal epidermoid carcinoma cells. Although TCS is a potential chemotherapeutic agent, its mechanism of action remains to be elucidated. In the present study, HEp-2 and AMC-HN-8 cells were treated with different concentrations of TCS combined with or without cisplatin. After 5 days of successive treatment, different experimental groups were detected using a cell counting kit-8 and the collected supernatants were analyzed using a lactate dehydrogenase kit. Flow cytometric assays were performed to detect apoptosis and cell cycle arrest in the HEp-2 and AMC-HN-8 cells, reverse transcription quantitative polymerase chain reaction was performed to detect the levels of p27, p21WAF and western blot analysis was performed to detect changes in c-Jun N-terminal protein kinase (JNK)/phosphorylated (phospho)-JNK, p38/phospho-p38, extracellular signal-regulated kinase (ERK)/phospho-ERK, caspase-3 and caspase-9 in the HEp-2 and AMC-HN-8 cancer cells. TCS significantly inhibited the cell viability of the HEp-2 and AMC-HN-8 cells, independently of necrosis. TCS induced apoptosis and increased the percentage of HEp-2 and AMC-HN-8 cells in the S-phase of the cell cycle. In addition, the JNK/mitogen-activated protein kinase (MAPK) pathway was activated by TCS in the HEp-2 and AMC-HN-8 cells. Low concentrations of TCS also induced apoptosis and S-phase cell cycle arrest in the HEp-2 and AMC-HN-8 cells. The antitumor effects of TCS may be associated with JNK/MAPK activation.
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PMID:Low concentrations of trichosanthin induce apoptosis and cell cycle arrest via c-Jun N-terminal protein kinase/mitogen-activated protein kinase activation. 2535 37