Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.36 (caspase-1)
 6,285 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine whether the apoptotic machinery of thyroid cancer cells is functional and could be activated for tumoricidal purposes, we examined the apoptosis induced by the cytokines TNF-alpha, Fas and TRAIL in thyroid cancer cell lines, NPA and SW579. Interestingly, out of these cytokines, only TRAIL was able to trigger significant apoptosis. The tumoricidal effect of TRAIL was further enhanced by CHX, suggesting the presence of CHX-sensitive inhibitor(s) of apoptosis in these thyroid cancer cell lines. The anti-apoptotic proteins like FLAME-1, Bcl-2 and Bcl-xL are believed to be such CHX-sensitive inhibitors in various types of cancer cells. We, however, provide the evidence using NPA and SW579 cell lines that these proteins were not affected by the CHX treatment in thyroid cancer cells. The apoptosis of thyroid cancer cells was mediated by the classical activation of caspases that in turn activated the DNA Fragmentation Factor (DFF-45). To elucidate the role of individual caspases in TRAIL-mediated apoptosis, the inhibitory effects of several general and specific tetrapeptide caspase inhibitors were studied. The inhibitors of caspase-1, -6, -8, and -9 as well as general upstream inhibitors of apoptosis could dramatically inhibit TRAIL-induced apoptosis in thyroid cancer cells. Caspase-2 and -3 inhibitors, on the other hand, had no significant effect. When the cells were treated with either agonistic Fas antibody (CH11) or TNF-alpha, no apoptotic changes were observed. The apoptosis induced by agonistic Fas Ab could be seen only after a prolonged exposure (24 h) to CHX, whereas TNF-alpha had no effect even in the presence of CHX. The efficacy of TRAIL was also tested on other types of thyroid cancer cells like ARO, FRO (anaplastic carcinoma) and TPC-1 (papillary carcinoma) and compared to that triggered by other death inducing cytokines FasL and TNF-alpha. Again TRAIL was more potent in triggering apoptosis than Fas and TNF-alpha. Since TRAIL is effective in selectively killing thyroid tumor cells without affecting normal thyrocytes and also does not cause organ toxicity and inflammation in vivo, its potential for the treatment of thyroid cancer seems very promising.
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PMID:TRAIL-induced apoptosis of thyroid cancer cells: potential for therapeutic intervention. 1091 93

Major intrinsic proteins (MIPs) form channels facilitating the passive transport of water and other small polar molecules across membranes. In this study, the complete open reading frame (ORF) of CiMIP1 (GenBank ID KY316061) encoding one kind of MIPs in the Antarctic ice microalga Chlamydomonas sp. ICE-L is successfully cloned using RACE. In addition, the expression patterns of CiMIP1 gene under different conditions of temperature and salinity are determined by qRT-PCR. The ORF of CiMIP1 gene encodes 308 amino acids, and the deduced amino acid sequence shows 74% homology with Chlamydomonas reinhardtii CrMIP1 (GenBank number 159471952). Phylogenetic analysis reveals that algal MIPs are divided into seven groups, and it is speculated that CiMIP1 most likely belongs to the MIPD subfamily. In addition, we are surprised to find that a third NPA motif exists at the carboxy terminus of the target protein except for two highly conserved ones. Expression analysis shows that the transcriptional levels of CiMIP1 gene are upregulated under either lower temperature or higher temperature and high salinity. In summary, the results together have provide new insights into the newly discovered gene in green algae and lay the foundation for further studies on the adaptation mechanism of Chlamydomonas sp. ICE-L to abiotic stresses.
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PMID:Molecular cloning and expression analysis of major intrinsic protein gene in Chlamydomonas sp. ICE-L from Antarctica. 2859 46