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221.
We have designed an efficient single step purification process using Resource RPC column in conjunction with triethyl amine/acetonitrile solvent system at similar pH at which the in vitro assembly of insulin is carried out from its two chains. The conditions have been optimized to separate native insulin from its single chain precursors as well as from other by-products. This method obviates the need of acidification, centrifugation, gel filtration, and concentration steps before HPLC purification of insulin from assembly mixture. The system offers wide pH stability, rapid regenerability, excellent pressure/flow characteristics, and high loading capacity. The authenticity and purity of human insulin purified by this procedure was evaluated by analytical reverse phase HPLC, peptide mapping, and isoelectric focusing. 相似文献
222.
Administration of CCl4 to normal rats and consequent oral feeding with ellagic acid (50 mg/kg) provided a significant protection against the biochemical alterations in serum and liver produced by CCl4. In vitro experiments showed that liver microsomes from animals treated with ellagic acid and CCl4, decreased lipid peroxidation compared to microsome prepared from rats exposed to CCl4 alone. 相似文献
223.
224.
In Shaker K(+) channels, formation of an electrostatic interaction between two charged residues, D316 and K374 in transmembrane segments S3 and S4, respectively, is a key step in voltage sensor biogenesis. Mutations D316K and K374E disrupt formation of the voltage sensor and lead to endoplasmic reticulum retention. We have now investigated the fates of these misfolded proteins. Both are significantly less stable than the wild-type protein. D316K is degraded by cytoplasmic proteasomes, whereas K374E is degraded by a lactacystin-insensitive, non-proteasomal pathway. Our results suggest that the D316K and K374E proteins are misfolded in recognizably different ways, an observation with implications for voltage sensor biogenesis. 相似文献
225.
226.
Idiopathic cases of male infertility from a region in India show low incidence of Y-chromosome microdeletion 总被引:2,自引:0,他引:2
Ambasudhan R Singh K Agarwal JK Singh SK Khanna A Sah RK Singh I Raman R 《Journal of biosciences》2003,28(5):605-612
Chromosomal and Y-chromosomal microdeletion analysis has been done in cases of idiopathic infertility with the objective of
evaluating the frequency of chromosomal and molecular anomaly as the causal factor of infertility. Barring a few cases of
Klinefelter syndrome (XXY or XY/XXY mosaics), no chromosomal anomaly was encountered. Y-microdeletion was analysed by PCR-screening
of STSs from different regions of the AZF (AZFa, AZFb, AZFc) on the long arm of the Y, as well as by using DNA probes of the
genes RBM, DAZ (Yq), DAZLA (an autosomal homologue of DAZ) and SRY (Yp; sex determining gene). Out of 177 cases examined,
9 (azoospermia -8 and oligoasthenospermia -1) showed partial deletion of AZF. The size of deletion varied among patients but
AZFc was either totally or partially removed in all of them. In contrast, no deletion was detected in AZFa. Testis biopsy
done on a limited number of cases (50) showed diverse stages of spermatogenic arrest with no specific correlation with the
genotype. The frequency of Y-chromosome microdeletion in our samples (∼ 5%) is much lower than the frequency (∼ 10%) reported
globally and the two previous reports from India. We contend that the frequency may be affected by population structures in
different geographical regions. 相似文献
227.
McClelland GB Khanna S González GF Butz CE Brooks GA 《Biochemical and biophysical research communications》2003,304(1):130-135
One of the many functions of liver peroxisomes is the beta-oxidation of long-chain fatty acids. It is essential for the continuation of peroxisomal beta-oxidation that a redox shuttle system exist across the peroxisomal membrane to reoxidize NADH. We propose that this redox shuttle system consists of a substrate cycle between lactate and pyruvate. Here we present evidence that purified peroxisomal membranes contain both monocarboxylate transporter 1 (MCT 1) and MCT 2 and that along with peroxisomal lactate dehydrogenase (pLDH) form a Peroxisomal Lactate Shuttle. Peroxisomal beta-oxidation was greatly stimulated by the addition of pyruvate and this increase was partially inhibited by the addition of the MCT blocker alpha-cyano-4-hydroxycinnamate (CINN). We also found that peroxisomes generated lactate in the presence of pyruvate. Together these data provide compelling that the Peroxisome Lactate Shuttle helps maintain organelle redox and the proper functioning of peroxisomal beta-oxidation. 相似文献
228.
Roy S Khanna S Wallace WA Lappalainen J Rink C Cardounel AJ Zweier JL Sen CK 《The Journal of biological chemistry》2003,278(47):47129-47135
Under normoxic conditions, pO2 ranges from 90 to <3 torr in mammalian organs with the heart at approximately 35 torr (5%) and arterial blood at approximately 100 torr. Thus, "normoxia" for cells is an adjustable variable. In response to chronic moderate hypoxia, cells adjust their normoxia set point such that reoxygenation-dependent relative elevation of pO2 results in perceived hyperoxia. We hypothesized that O2, even in marginal relative excess of the pO2 to which cells are adjusted, results in the activation of specific O2-sensitive signal transduction pathways that alter cellular phenotype and function. Thus, reperfusion causes damage to the tissue at the focus of ischemia while triggering remodeling in the peri-infarct region by means of perceived hyperoxia. We reported first evidence demonstrating that perceived hyperoxia triggers the differentiation of cardiac fibroblasts (CF) to myofibroblasts by a p21-dependent mechanism (Roy, S., Khanna, S., Bickerstaff, A. A., Subramanian, S. V., Atalay, M., Bierl, M., Pendyala, S., Levy, D., Sharma, N., Venojarvi, M., Strauch, A., Orosz, C. G., and Sen, C. K. (2003) Circ. Res. 92, 264-271). Here, we sought to characterize the genomic response to perceived hyperoxia in CF using GeneChips trade mark. Candidate genes were identified, confirmed and clustered. Cell cycle- and differentiation-associated genes represented a key target of perceived hyperoxia. Bioinformatics-assisted pathway reconstruction revealed the specific signaling processes that were sensitive to perceived hyperoxia. To test the significance of our in vitro findings, a survival model of rat heart focal ischemia-reperfusion (I-R) was investigated. A significant induction in p21 mRNA expression was observed in I-R tissue. The current results provide a comprehensive molecular definition of perceived hyperoxia in cultured CF. Furthermore, the first evidence demonstrating activation of perceived hyperoxia sensitive genes in the cardiac I-R tissue is presented. 相似文献
229.
Ataxia-telangiectasia-mutated (ATM) and NBS1-dependent phosphorylation of Chk1 on Ser-317 in response to ionizing radiation 总被引:24,自引:0,他引:24
Gatei M Sloper K Sorensen C Syljuäsen R Falck J Hobson K Savage K Lukas J Zhou BB Bartek J Khanna KK 《The Journal of biological chemistry》2003,278(17):14806-14811
In mammals, the ATM (ataxia-telangiectasia-mutated) and ATR (ATM and Rad3-related) protein kinases function as critical regulators of the cellular DNA damage response. The checkpoint functions of ATR and ATM are mediated, in part, by a pair of checkpoint effector kinases termed Chk1 and Chk2. In mammalian cells, evidence has been presented that Chk1 is devoted to the ATR signaling pathway and is modified by ATR in response to replication inhibition and UV-induced damage, whereas Chk2 functions primarily through ATM in response to ionizing radiation (IR), suggesting that Chk2 and Chk1 might have evolved to channel the DNA damage signal from ATM and ATR, respectively. We demonstrate here that the ATR-Chk1 and ATM-Chk2 pathways are not parallel branches of the DNA damage response pathway but instead show a high degree of cross-talk and connectivity. ATM does in fact signal to Chk1 in response to IR. Phosphorylation of Chk1 on Ser-317 in response to IR is ATM-dependent. We also show that functional NBS1 is required for phosphorylation of Chk1, indicating that NBS1 might facilitate the access of Chk1 to ATM at the sites of DNA damage. Abrogation of Chk1 expression by RNA interference resulted in defects in IR-induced S and G(2)/M phase checkpoints; however, the overexpression of phosphorylation site mutant (S317A, S345A or S317A/S345A double mutant) Chk1 failed to interfere with these checkpoints. Surprisingly, the kinase-dead Chk1 (D130A) also failed to abrogate the S and G(2) checkpoint through any obvious dominant negative effect toward endogenous Chk1. Therefore, further studies will be required to assess the contribution made by phosphorylation events to Chk1 regulation. Overall, the data presented in the study challenge the model in which Chk1 only functions downstream from ATR and indicate that ATM does signal to Chk1. In addition, this study also demonstrates that Chk1 is essential for IR-induced inhibition of DNA synthesis and the G(2)/M checkpoint. 相似文献
230.
Patra A Batra S Bhaduri AP Khanna A Chander R Dikshit M 《Bioorganic & medicinal chemistry》2003,11(10):2269-2276
The synthesis of isoxazole-based derivatives utilizing Baylis-Hillman chemistry and results of their preliminary bioevaluation as hypolipidemic agents in triton model are described. 相似文献