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1.
Pasupathi Sundaramoorthy Jae Jun Sim Yeong-Su Jang Siddhartha Kumar Mishra Keun-Yeong Jeong Poonam Mander Oh Byung Chul Won-Sik Shim Seung Hyun Oh Ky-Youb Nam Hwan Mook Kim 《PloS one》2015,10(1)
Cancer cell motility is a key phenomenon regulating invasion and metastasis. Focal adhesion kinase (FAK) plays a major role in cellular adhesion and metastasis of various cancers. The relationship between dietary supplementation of calcium and colon cancer has been extensively investigated. However, the effect of calcium (Ca2+) supplementation on calpain-FAK-motility is not clearly understood. We sought to identify the mechanism of FAK cleavage through Ca2+ bound lactate (CaLa), its downstream signaling and role in the motility of human colon cancer cells. We found that treating HCT116 and HT-29 cells with CaLa immediately increased the intracellular Ca2+ (iCa2+) levels for a prolonged period of time. Ca2+ influx induced cleavage of FAK into an N-terminal FAK (FERM domain) in a dose-dependent manner. Phosphorylated FAK (p-FAK) was also cleaved in to its p-N-terminal FAK. CaLa increased colon cancer cells motility. Calpeptin, a calpain inhibitor, reversed the effects of CaLa on FAK and pFAK cleavage in both cancer cell lines. The cleaved FAK translocates into the nucleus and modulates p53 stability through MDM2-associated ubiquitination. CaLa-induced Ca2+ influx increased the motility of colon cancer cells was mediated by calpain activity through FAK and pFAK protein destabilization. In conclusion, these results suggest that careful consideration may be given in deciding dietary Ca2+ supplementation to patient undergoing treatment for metastatic cancer. 相似文献
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Disturbance plays an integral part in generating heterogeneity required for ecosystem persistence, but the increased amplitude and duration of disturbances linked to drivers of global change could result in ecosystem shifts or collapse. Biomonitoring over time provides insights into trajectories of ecosystem change. The responses of two instream animal taxa to two contrasting disturbance events, a major flood event and the long-term cumulative effects of land-use changes, were assessed in 1999–2012 by quantifying variation and change in abundance of functional groups based on flow rate sensitivity, water quality and metrics of ecological condition. All metrics recovered to pre-flood conditions within seven months after the flood event. Similarly, cumulative impacts of land use effected significant decreases in some but not all metrics. Indices that did not change, including SASS total score and ASPT, were the result of insufficient consideration of the decrease in the abundance of sensitive taxa specifically, and the abundance of all taxa in general. The decrease in abundance of sensitive taxa could signal imminent collapse in certain metrics. Evidence is also provided for a shift in the structure of fish assemblages linked to the decrease and loss of taxa sensitive to ecosystem degradation caused by the longer-term impacts of land-use change. 相似文献
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G Henderson A Duncan M Kromberg J Roberts F Sim G Vafidis 《BMJ (Clinical research ed.)》1990,300(6731):1076
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S Y Lee S S Sim J W Kim K H Moon J H Kim S G Rhee 《The Journal of biological chemistry》1990,265(16):9434-9440
A new, rapid method for purification of inositol(1,4,5)P3 3-kinase in high yield from rat brain is described. Purified enzyme exhibited a polypeptide of Mr = 53,000 on sodium dodecyl sulfate-polyacrylamide gel and a specific activity of 29 mumol/min/mg at 37 degrees C in the absence of calmodulin. Inclusion of calpain inhibitors was critical for obtaining the 53-kDa protein as the major product and 0.1% of the zwitterionic detergent, 3-[(3-cholamidopropyl)dimethylamino]-2-propanesulfonate, was necessary to stabilize enzyme activity. In the absence of calpain inhibitors, the 53-kDa protein degraded progressively during purification and yielded a mixture containing polypeptides of various sizes. Relative intensity of these degradation products on sodium dodecyl sulfate-polyacrylamide gel varied from one preparation to another. However, broad band(s) at the 42-45 kDa region and a band at 35 kDa were always weak, while bands of 53, 51, 40 (sometimes doublets), 33, and 32 KDa were usually strong. The fact that all of these polypeptides including the weak bands of 42-45 and 35 kDa were derived from the 53 kDa form was confirmed by their immunocross-reactivity with monoclonal antibodies to the 53 kDa form. When the 51, 40, and a mixture of the 33 and 32 kDa forms were obtained separately and nearly free from other forms, each of them exhibited catalytic activity. Nevertheless, calmodulin binds to polypeptides larger than 35,000 but not to the 33 and 32 kDa forms. Incubation of the purified 53 kDa form with calpain generated a fragmentation pattern nearly identical to that generated during purification in the absence of calpain inhibitors. Incubation with five other endoproteases produced proteolytic fragments slightly different from those by calpain. However, the general fragmentation patterns generated by the proteases were similar, suggesting that inositol(1,4,5)P3 3-kinase contains several motifs susceptible to a variety of proteases. 相似文献
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Katarina Nilsson Anna Flysjö Jennifer Davis Sarah Sim Nicole Unger Simon Bell 《The International Journal of Life Cycle Assessment》2010,15(9):916-926
Purpose
The goal of the study was to compare the environmental impact of butter and margarine. Altogether, seven products were studied in three European markets: UK, Germany and France. 相似文献8.
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The plasma complement protein C4 is encoded at two highly polymorphic loci, A and B, within the class-III region of the major histocompatibility complex. At least 34 different polymorphic variants of human C4 have been identified, including non-expressed or 'null' alleles. The main method of identification of C4 polymorphic allotypes is separation on the basis of charge by agarose-gel electrophoresis of plasma. On staining by immunofixation with anti-C4 antibodies, each C4 type gives three major bands, but, since individuals can have up to five allotypes, the overlapping banding pattern is difficult to interpret. We show that digestion of plasma samples with carboxypeptidase B, which removes C-terminal basic amino acids, before electrophoresis, produces a single, sharp, distinct band for each allotype and allows identification of the biochemical basis of the multiple banding pattern previously observed in C4 phenotype determination. 相似文献