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971.
Diana Walluscheck Kathrin Reissig Khuloud Bajbouj Oliver Ullrich Roland Hartig Hala Gali‐Muhtasib Antje Diestel Albert Roessner Regine Schneider‐Stock 《Journal of cellular and molecular medicine》2011,15(7):1528-1541
Besides the well‐understood DNA damage response via establishment of G2 checkpoint arrest, novel studies focus on the recovery from arrest by checkpoint override to monitor cell cycle re‐entry. The aim of this study was to investigate the role of Chk1 in the recovery from G2 checkpoint arrest in HCT116 (human colorectal cancer) wt, p53–/– and p21–/– cell lines following H2O2 treatment. Firstly, DNA damage caused G2 checkpoint activation via Chk1. Secondly, overriding G2 checkpoint led to (i) mitotic slippage, cell cycle re‐entry in G1 and subsequent G1 arrest associated with senescence or (ii) premature mitotic entry in the absence of p53/p21WAF1 causing mitotic catastrophe. We revealed subtle differences in the initial Chk1‐involved G2 arrest with respect to p53/p21WAF1: absence of either protein led to late G2 arrest instead of the classic G2 arrest during checkpoint initiation, and this impacted the release back into the cell cycle. Thus, G2 arrest correlated with downstream senescence, but late G2 arrest led to mitotic catastrophe, although both cell cycle re‐entries were linked to upstream Chk1 signalling. Chk1 knockdown deciphered that Chk1 defines long‐term DNA damage responses causing cell cycle re‐entry. We propose that recovery from oxidative DNA damage‐induced G2 arrest requires Chk1. It works as cutting edge and navigates cells to senescence or mitotic catastrophe. The decision, however, seems to depend on p53/p21WAF1. The general relevance of Chk1 as an important determinant of recovery from G2 checkpoint arrest was verified in HT29 colorectal cancer cells. 相似文献
972.
应用PCR的技术从质粒pAIFN中扩增人干扰素α-2b(Human interferon α-2b,HuIFN α-2b)编码基因,将其连接到pBI121双元载体构建植物真核表达载体pBIFN;用冻融法将该载体转染根癌农杆菌LBA4404;并用叶盘浸染法转化烟草叶片,经转化的烟草叶片的组织培养,诱导愈伤获得再生植株。通过应用PCR,RT-PCR,Wes-tern blot和WISH/VSV方法检测获得的烟草再生植株,结果表明HuIFN α-2b基因已成功整合进烟草核基因组并表达出具有活性的HuIFN α-2b蛋白。本文对HuIFN α-2b基因在烟草核系统中的表达进行了研究,为进一步在烟草叶绿体系统中该基因的表达研究奠定了基础。 相似文献
973.
974.
Mark B. Bushuev Viktor P. Krivopalov Dmitrii Yu. Naumov Katerina A. Vinogradova Lilia A. Sheludyakova Stanislav V. Larionov 《Inorganica chimica acta》2010,363(7):1547-13900
A new bidentate chelating pyrazolylpyrimidine ligand bearing a strong electron-donating substituent, i.e. 4-(3,5-diphenyl-1H-pyrazol-1-yl)-6-(piperidin-1-yl)pyrimidine (L) (Scheme 1), has been synthesized and used to obtain the copper(II) complexes by reaction with CuCl2. The molar ratio Cu:L = 1:2 leads to isolation of a complex having CuL2Cl2 empirical formula, while the molar ratio Cu:L = 1:1 gives a complex with CuLCl2 empirical formula. The crystal structure of L as well as the structures of both complexes were studied by single crystal X-ray diffraction. The crystal structure of CuL2Cl2 compound is formed by trans-[CuL2Cl2] mononuclear molecules. Surprisingly, in contrast to the previous compound having molecular structure, the crystal structure of CuLCl2 consists of mononuclear [CuL2Cl]+ complex cations and dinuclear [Cu2Cl6]2− anions. Thus, formula of CuLCl2 complex can be represented as [CuL2Cl]2[Cu2Cl6]. In both complexes molecules of L adopt bidentate chelating coordination mode through N2 atom of pyrazole and N3 atom of pyrimidine rings forming five-membered CuN3C metallocycles. Owing to C-H···N interactions and π-π-stacking L molecules form 2D network. In the structure of trans-[CuL2Cl2] there exist double lone pair(N(piperidine))-π(pyrimidine) interactions and C-H···Cl contacts resulting in the formation of 1D chains. Layered 2D structure of [CuL2Cl]2[Cu2Cl6] results from C-H···Cl, C-H···π and double lone pair(Cl([CuL2Cl]+ complex cation)-π(pyrimidine) interactions. 相似文献
975.
976.
Takashi Arakawa Yoshiaki Kamiya 《Biochemical and biophysical research communications》2010,397(2):345-349
We previously reported the identification of DP-1 isoforms (α and β), which are structurally C-terminus-deleted ones, and revealed the low-level expression of these isoforms. It is known that wild-type DP-1 is degraded by the ubiquitin-proteasome system, but few details are known about the domains concerned with the protein stability/instability for the proteolysis of these DP-1 isoforms. Here we identified the domains responsible for the stability/instability of DP-1. Especially, the DP-1 “Stabilon” domain was a C-terminal acidic motif and was quite important for DP-1 stability. Moreover, we propose that this DP-1 Stabilon may be useful for the stability of other nuclear proteins when fused to them. 相似文献
977.
Dogs demonstrate an age-related cognitive decline, which may be related to a decrease in the concentration of omega-3 polyunsaturated
fatty acids (n-3 PUFA) in the brain. Medium chain triglycerides (MCT) increase fatty acid oxidation, and it has been suggested that this
may raise brain n-3 PUFA levels by increasing mobilization of n-3 PUFA from adipose tissue to the brain. The goal of the present study was to determine whether dietary MCT would raise n-3 PUFA concentrations in the brains of aged dogs. Eight Beagle dogs were randomized to a control diet (n = 4) or an MCT (AC-1203) enriched diet (n = 4) for 2 months. The animals were then euthanized and the parietal cortex was removed for phospholipid, cholesterol and
fatty acid determinations by gas-chromatography. Dietary enrichment with MCT (AC-1203) resulted in a significant increase
in brain phospholipid and total lipid concentrations (P < 0.05). In particular, n-3 PUFA within the phospholipid, unesterified fatty acid, and total lipid fractions were elevated in AC-1203 treated subjects
as compared to controls (P < 0.05). Brain cholesterol concentrations did not differ significantly between the groups (P > 0.05). These results indicate that dietary enrichment with MCT, raises n-3 PUFA concentrations in the parietal cortex of aged dogs. 相似文献
978.
四氯化碳诱导的小鼠肝纤维化模型中SDF-1/αCXCR4的表达及其意义 总被引:1,自引:0,他引:1
目的检测四氯化碳(CCl4)诱导的肝纤维化小鼠模型肝脏SDF-1/αCXCR4的表达,评价SDF-1/αCXCR4轴与肝纤维化的关系,为研究肝纤维化肝损伤发生及损伤修复机制研究提供基础。方法选用6周龄雌性纯系C57小鼠,采用40%的CCl4/橄榄油溶液腹腔注射,剂量为1 mL/kg,每周2次,共4周,制成肝纤维化模型,取肝纤维化及正常对照组小鼠肝脏标本,采用RT-PCR及免疫组化检测SDF-1α的表达,采用RT-PCR及Western检测CXCR4受体的表达。结果与对照组相比,SDF-1α及CXCR4在肝纤维化模型小鼠肝脏组织中的表达较对照组明显上调,差异具有统计学意义(P〈0.05)。结论肝纤维小鼠肝组织的SDF-1/αCXCR4受体表达上调,为研究肝纤维化肝损伤机制及干细胞移植治疗提供理论基础。 相似文献
979.
目的:研究HIF-1α、PHDs及OS-9的表达变化在低氧性肺动脉高压(HPH)中的作用和意义。方法:SD大鼠随机分5组(n=8);对照组(C组)和低氧3、7、14和21d组,常压低氧复制HPH大鼠模型。原位杂交、RT-PCR检测mRNA表达,免疫组化、Westernblot检测蛋白质表达。结果:①HIF-1αmRNA对照纽和低氧3d无明显差异,低氧14d后表达明显增高;HIF-1α蛋白质低氧3d组表达明显增高,7d达高峰;②对照组PHD1mRNA呈阳性表达,各低氧组与对照组比较差异不显著,PHD1蛋白质在对照组强阳性表达,低氧14d下降,低氧21d保持较低水平;对照组PHD2mRNA呈阳性表达,低氧3d增高,14d达到高峰,21d维持高水平,其蛋白质表达趋势与mRNA相同;对照组PHD3mRNA和蛋白质表达不明显,低氧3dmRNA明显增高,蛋白质低氧3d明显增高,低氧7d保持高水平,低氧14d和21d下降。③OS-9mRNA在对照组呈强阳性表达,低氧3d后迅速降低,14d达到最低水平;其蛋白质表达趋势与mRNA相同。相关分析表明,肺小动脉壁OS-9蛋白质表达水平与OS-9mRNA呈正相关,与RVHI、mPAP、WA%及LA%呈负相关。结论:HIF-1α、PHDs及OS-9均在大鼠HPH的发病机制中发挥作用。OS-9可能通过增强PHDs的活性来调节HIF-1α的表达,从而在HPH的发生和发展中发挥作用。 相似文献
980.
Mice lacking Niemann-Pick C1-Like 1 (NPC1L1) (NPC1L1(-/-)mice) exhibit a defect in intestinal absorption of cholesterol and phytosterols. However, wild-type (WT) mice do not efficiently absorb and accumulate phytosterols either. Cell-based studies show that NPC1L1 is a much weaker transporter for phytosterols than cholesterol. In this study, we examined the role of NPC1L1 in phytosterol and cholesterol trafficking in mice lacking ATP-binding cassette (ABC) transporters G5 and G8 (G5/G8(-/-) mice). G5/G8(-/-) mice develop sitosterolemia, a genetic disorder characterized by the accumulation of phytosterols in blood and tissues. We found that mice lacking ABCG5/G8 and NPC1L1 [triple knockout (TKO) mice] did not accumulate phytosterols in plasma and the liver. TKO mice, like G5/G8(-/-) mice, still had a defect in hepatobiliary cholesterol secretion, which was consistent with TKO versus NPC1L1(-/-) mice exhibiting a 52% reduction in fecal cholesterol excretion. Because fractional cholesterol absorption was reduced similarly in NPC1L1(-/-) and TKO mice, by subtracting fecal cholesterol excretion in TKO mice from NPC1L1(-/-) mice, we estimated that a 25g NPC1L1(-/-) mouse may secrete about 4 mumol of cholesterol daily via the G5/G8 pathway. In conclusion, NPC1L1 is essential for phytosterols to enter the body in mice. 相似文献