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71.
Seon-Yeong Kwak Briony E. Forbes Yoon-Sik Lee Alessia Belgi John D. Wade Mohammed Akhter Hossain 《International journal of peptide research and therapeutics》2010,16(3):153-158
Numerous analogues of insulin have been prepared over the past three decades for use in diabetic therapy. However, only two long-acting insulins have been approved for clinical use. One is Levemir (Novo Nordisk) and the other is Lantus (Sanofi-Aventis). Glargine (commercial name: Lantus) is characterized by a substitution of Gly in place of Asn at the C terminus of the A-chain and addition of two Arg residues to the C terminus of the B-chain. Despite the clinical advantages of glargine, it is not without concern that its increased affinity for the IGF-1 receptor may correlate with increased mitogenic activity. Recently, a systematic study of modified analogues of glargine showed that placement of an extra Arg residue at the N terminus of the A-chain conferred improved insulin:IGF-1 receptor selectivity without significant loss of pharmacological profile. However, as it is difficult to prepare such an analogue in high yield by recombinant DNA methods, we undertook its chemical assembly by our refined solid phase synthesis method. We describe herein its chemical preparation and biological activity in both insulin receptor binding assays and DNA synthesis assays. The synthetic analogue, A0:R glargine, showed slightly reduced affinity for IR-B (twofold) compared to native insulin. In stimulating DNA synthesis, A0:R glargine was slightly less potent compared to insulin or glargine. This result ultimately confirms the previous report that A0:R glargine has a lower potency in mitogenic assays compared to glargine. This glargine analogue thus could be a potential lead compound for drug design and development for the treatment of diabetes. 相似文献
72.
Seonyoung Choi So‐Young Park Ji Jeong Eunkyung Cho Sohee Phark Min Lee Dongsub Kwak Ji‐Youn Lim Woon‐Won Jung Donggeun Sul 《Proteomics》2010,10(9):1831-1846
The effects of di(2‐ethylhexyl) phthalate (DEHP) on proteins secreted by HepG2 cells were studied using a proteomic approach. HepG2 cells were exposed to various concentrations of DEHP (0, 2.5, 5, 10, 25, 50, 100, and 250 μM) for 24 or 48 h. 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) and comet assays were then conducted to determine the cytotoxicity and genotoxicity of DEHP, respectively. The MTT assay showed that 10 μM DEHP was the maximum concentration that did not cause cell death. In addition, the DNA damage in HepG2 cells exposed to DEHP was found to increase in a dose‐ and time‐dependent fashion. Proteomic analysis using two different pI ranges (4–7 and 6–9) and large size 2‐DE revealed the presence of 2776 protein spots. A total of 35 (19 up‐ and 16 down‐regulated) proteins were identified as biomarkers of DEHP by ESI‐MS/MS. Several differentiated protein groups were also found. Proteins involved in apoptosis, transportation, signaling, energy metabolism, and cell structure and motility were found to be up‐ or down‐regulated. Among these, the identities of cystatin C, Rho GDP inhibitor, retinol binding protein 4, gelsolin, DEK protein, Raf kinase inhibitory protein, triose phosphate isomerase, cofilin‐1, and haptoglobin‐related protein were confirmed by Western blot assay. Therefore, these proteins could be used as potential biomarkers of DEHP and human disease associated with DEHP. 相似文献
73.
Geun-Hee Kwak Hwa-Young Kim 《Biochemical and biophysical research communications》2010,395(3):412-227
Free methionine-R-sulfoxide reductase (fRMsr) is a new type of methionine sulfoxide reductase that catalyzes the reduction of free methionine-R-sulfoxide to methionine. This enzyme cannot reduce oxidized methionine residues in proteins. While three Cys residues, Cys-91, Cys-101 and Cys-125, have been demonstrated to be involved in the catalysis by Saccharomyces cerevisiae fRMsr, their specific functions have not been fully established. In this work, we performed in vivo growth complementation experiments using S. cerevisiae cells lacking all three known methionine sulfoxide reductases. Cells containing a C125S construct, in which Cys-125 in fRMsr was replaced with Ser, did not grow in methionine sulfoxide medium, whereas cells containing C91S, C101S, or C91/101S constructs could grow in this medium. In addition, when assayed with thioredoxin and glutaredoxin reduction systems, the C125S form was inactive, whereas C91S and C101S had 1-2% and 9-10%, respectively, of the activity of the wild-type fRMsr. These data show that Cys-125 is the catalytic residue in fRMsr. 相似文献
74.
? Premise of the study: Embryonic inbreeding depression is a key influence on mating system evolution and can be difficult to estimate in self-incompatible species. A pollen chase experiment was used to estimate the magnitude of embryonic inbreeding depression in Costa Rican Witheringia solanacea, a species polymorphic for self-incompatibility (SI). In a pollen chase experiment, bud self-pollinations are followed after anthesis by outcross pollinations, with a comparable pair of outcross pollinations used as a control. Lowered seed set for the self-precedence treatment indicates embryonic inbreeding depression. ? Methods: Embryonic inbreeding depression was assayed for self-compatible (SC) individuals and for SI plants from two populations that differ quantitatively in the onset and enzymatic activity of their SI response. Microsatellite markers were used to assay the selfing rate of a sample of surviving progeny from the prior self-pollination treatment. ? Key results: SC individuals showed no evidence of embryonic inbreeding depression. In SI plants, prior self-pollination reduced seed number by 28-70%, depending on population. Microsatellite genotyping revealed that embryonic inbreeding depression was even more severe than estimated by the phenotypic data: for mature fruits resulting from self-pollination precedence, the majority of the progeny were the result of outcross fertilization. ? Conclusions: Lineage-specific purging of recessive lethals has accompanied the evolution of SC in this species. SI populations show contrasting levels of embryonic inbreeding depression, with nearly complete embryonic lethality upon selfing in the Monteverde population. In the face of high embryonic inbreeding depression, an increase in selfing rate can evidently occur only under severe pollen limitation. 相似文献
75.
76.
Su Jung Park Kyung Jin Kwak Hyun Ju Jung Hwa Jung Lee Hunseung Kang 《Phytochemistry》2010,71(5-6):543-547
Among the four cold shock domain proteins (CSDPs) identified in Arabidopsis thaliana, it has recently been shown that CSDP1 harboring seven CCHC-type zinc fingers, but not CSDP2 harboring two CCHC-type zinc fingers, function as a RNA chaperone during cold adaptation. However, the structural features relevant to this differing RNA chaperone activity between CSDP1 and CSDP2 remain largely unknown. To determine which structural features are necessary for the RNA chaperone activity of the CSDPs, the importance of the N-terminal cold shock domain (CSD) and the C-terminal zinc finger glycine-rich domains of CSDP1 and CSDP2 were assessed. The results of sequence motif-swapping and deletion experiments showed that, although the CSD itself harbored RNA chaperone activity, the number and length of the zinc finger glycine-rich domains of CSDPs were crucial to the full activity of the RNA chaperones. The C-terminal domain itself of CSDP1, harboring seven CCHC-type zinc fingers, also has RNA chaperone activity. The RNA chaperone activity and nuclei acid-binding property of the native and chimeric proteins were closely correlated with each other. Collectively, these results indicate that a specific modular arrangement of the CSD and the zinc finger domain determines both the RNA chaperone activity and nucleic acid-binding property of CSDPs; this, in turn, contributes to enhanced cold tolerance in plants as well as in bacteria. 相似文献
77.
Stable isotopes can be used to elucidate ecological relationships in community and trophic studies. Findings are calibrated
against baselines, e.g. from a producer or primary consumer, assumed to act as a reference to the isotopic context created
by spatio-temporal attributes such as geography, climate, nutrient, and energy sources. The ability of an organism to accurately
represent a community base depends on how, and over what time-scale, it assimilates ambient materials. Freshwater mussels
have served as references for trophic studies of freshwater communities and as indicators of change in nutrient pollution
load or source. Their suitability as reference animals has not yet been fully explored, however. We conducted a series of
studies examining the suitability of freshwater mussels as isotopic baselines, using their ability to reflect variation in
ambient nutrient loads as a case scenario. (1) We analyzed bivalve foot tissue δ15N and δ13C from 22 stream reaches in the Piedmont region of North Carolina, USA to show that compositions varied substantially among
locations. Site mean bivalve δ13C values correlated with site ambient particulate organic matter (POM) δ13C values, and site mean bivalve δ15N values correlated with site ambient water dissolved δ15N-NO3 values. (2) Similarity of results among sample types demonstrated that the minimally invasive hemolymph sample is a suitable
substitute for foot tissue in δ15N analyses, and that small sample sizes generate means representative of a larger population. Both findings can help minimize
the impact of sampling on imperiled freshwater mussel populations. (3) In a bivalve transplantation study we showed that hemolymph
δ15N compositions responded to a shift in ambient dissolved δ15N-NO3, although slowly. The tissue turnover time for bivalve hemolymph was 113 days. We conclude that bivalves serve best as biomonitors
of chronic, rather than acute, fluctuations in stream nutrient loads, and provide initial evidence of their suitability as
time-integrated isotopic baselines for community studies. 相似文献
78.
79.
Yu HN Song EK Yoo SM Lee YR Han MK Yim CY Kwak JY Kim JS 《Biochemical and biophysical research communications》2007,354(3):764-768
The ADP-ribose (ADPR) pyrophosphatase (ADPRase) NUDT5, a member of a superfamily of Nudix hydrolases, hydrolyzes ADP-ribose (ADPR) to AMP and ribose 5'-phosphate. Nitric oxide (NO) enhances nonenzymatic ADP-ribosylation of proteins such as beta-actin and glyceraldehydes 3-phosphate dehydrogenase in the presence of free ADPR, suggesting a possibility that NUDT5 could also be ADP-ribosylated by its substrate, ADPR. Here, we show that NO stimulates nonenzymatic ADP-ribosylation of NUDT5 using ADP-ribose and consequently activates its ADPRase activity. We found that ADPRase activity in J774 macrophage cells is increased by the treatment with SNP, an exogenous NO generator or TNF-alpha/IFN-gamma, endogenous NO inducers. Anti-NUDT5 antibody pulled down most of the ADPRase activity increased by NO, indicating that the ADPRase regulated by NO is NUDT5. Using recombinant human NUDT5, we also demonstrated that the increase of ADPRase activity is mediated via ADP-ribosylation at cysteine residue(s) in the presence of reductant. This result suggests that NO activates NUDT5 through ADP-ribosylation at cysteine residues of the enzyme in macrophages. 相似文献
80.
DNA-methyltransferase-3B (DNMT3b) plays an important role in the generation of aberrant methylation in carcinogenesis. DNMT3b SNP has been associated with susceptibility to lung, head, neck, and breast cancer, but its association with the development
of colon cancer has not been reported. We investigated the relationship between the 39179GT polymorphism in the DNMT3b gene, which is involved in de novo methylation and is associated with the risk of adenocarcinoma of the colon in Koreans.
The DNMT3b 39179GT genotypes were determined by a PCR-RFLP method in 248 adenocarcinomas of colon cancer patients and in 248 healthy
controls matched as to age and sex. When stratified by sex and age, a significantly reduced risk of the combined GT and GG
genotypes was observed in younger patients (<59, adjusted OR = 0.255, 95% CI = 0.133–0.489) and in male patients (adjusted
OR = 0.383, 95% CI = 0.225–0.652). The DNMT3b 39179GT polymorphism may be a genetic determinant of adenocarcinoma of the colon, especially in younger Korean men. 相似文献