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971.
Lina Du Robert W. Hickey H��lya Bayir Simon C. Watkins Vladimir A. Tyurin Fengli Guo Patrick M. Kochanek Larry W. Jenkins Jin Ren Greg Gibson Charleen T. Chu Valerian E. Kagan Robert S. B. Clark 《The Journal of biological chemistry》2009,284(4):2383-2396
Sex-dependent differences in adaptation to famine have long been
appreciated, thought to hinge on female versus male preferences for
fat versus protein sources, respectively. However, whether these
differences can be reduced to neurons, independent of typical nutrient depots,
such as adipose tissue, skeletal muscle, and liver, was heretofore unknown. A
vital adaptation to starvation is autophagy, a mechanism for recycling amino
acids from organelles and proteins. Here we show that segregated neurons from
males in culture are more vulnerable to starvation than neurons from females.
Nutrient deprivation decreased mitochondrial respiration, increased
autophagosome formation, and produced cell death more profoundly in neurons
from males versus females. Starvation-induced neuronal death was
attenuated by 3-methyladenine, an inhibitor of autophagy; Atg7
knockdown using small interfering RNA; or l-carnitine, essential
for transport of fatty acids into mitochondria, all more effective in neurons
from males versus females. Relative tolerance to nutrient deprivation
in neurons from females was associated with a marked increase in triglyceride
and free fatty acid content and a cytosolic phospholipase A2-dependent
increase in formation of lipid droplets. Similar sex differences in
sensitivity to nutrient deprivation were seen in fibroblasts. However,
although inhibition of autophagy using Atg7 small interfering RNA
inhibited cell death during starvation in neurons, it increased cell death in
fibroblasts, implying that the role of autophagy during starvation is both
sex- and tissue-dependent. Thus, during starvation, neurons from males more
readily undergo autophagy and die, whereas neurons from females mobilize fatty
acids, accumulate triglycerides, form lipid droplets, and survive longer.Sex-dependent differences in adaptation to famine have long been
appreciated (1,
2), thought to hinge on a
female preference for fat sources, in contrast to a male preference for
protein sources (3). Fatty acid
metabolism is different between sexes normally
(4) and under conditions of
starvation (1,
2). During exercise, in
addition to increases in carbohydrate requirement, men increase their need for
amino acids, whereas women increase mobilization of fat
(5). Furthermore, sex-dependent
responses to nutritional stress associated with either self-induced weight
loss or illness-related cachexia also exist
(6,
7).An important adaptation to starvation is autophagy (autophagy-associated
proteins, abbreviated ATG). Classic, starvation-induced autophagy is initiated
by nutrient and amino acid deprivation, glucagon, and cAMP
(8,
9). ATG7, a ubiquitin E1-like
enzyme, is essential for autophagy, with phosphorylation of preautophagosomal
membranes, formation of ATG12-ATG5 complexes, and processing of ATG8/LC3
(microtubule-associated protein light chain-3) as other crucial steps in this
process (10).
Starvation-induced autophagy is regulated by class III phosphatidylinositol
3-kinase and the Bcl-2-interacting partner, Beclin-1
(11). The autophagosomes then
engulf cytoplasmic material and/or organelles, such as mitochondria, the
latter sometimes referred to as “mitophagy,” disassembling large
proteins and organelles to recycle amino acids and other nutrients, an
important response to starvation
(12).It is unknown whether starvation can induce autophagy in the brain;
however, there is evidence that critical starvation can result in brain
atrophy in humans. It has been reported that ∼30% of people during a
prolonged hunger strike (mean of 199 days) will show brain tissue loss
(13), and brain shrinkage in
patients with anorexia nervosa is well documented
(14,
15). Although 48 h of food
deprivation does not produce detectable autophagy in brains from mice
(16), the aforementioned
reports are consistent with long durations of starvation as a bona
fide stimulus for autophagy in brain. There are recent studies suggesting
that other stimuli can induce autophagy in the brain, such as trauma
(17) and ischemia
(18), and that autophagy may
contribute to neuronal death. There is also evidence for autophagy in the
human brain after trauma and critical illness
(19), which probably includes
both elements of malnutrition and systemic stress. A potential role for brain
atrophy as a contributor to neurological morbidity in the critically ill and
injured is an emerging topic
(20). 相似文献
972.
UV-B滤减处理下烟草光合作用参数对光照度的响应 总被引:3,自引:0,他引:3
以烟草栽培品种K326为材料,通过覆盖不同的透明薄膜滤减UV-B辐射,研究了100%(CK)、75%(T1)、50% (T2)、35%(T3)UV-B辐射透过率处理下,烟草成熟初期光合参数与50和150 cm高度光照度的关系。结果表明:对于T1、T3,烟叶净光合速率的变化主要是气孔因素,而T2主要是非气孔因素;通过对4类处理的平均水分利用效率的比较,发现可能存在一个UV-B辐射对水分利用效率影响的阈值范围;150 cm高度光照度除了对蒸腾速率和T2处理的气孔导度起促进作用外,对其他光合参数都有一定的抑制作用;而不同处理的烟叶光合参数对50和150 cm高度上的光照度的响应都较为一致,在敏感程度上则存在差异。 相似文献
973.
Guang Liang Lili Shao Yi Wang Chengguang Zhao Yanhui Chu Jian Xiao Yu Zhao Xiaokun Li Shulin Yang 《Bioorganic & medicinal chemistry》2009,17(6):2623-2631
Curcumin has a surprisingly wide range of chemo-preventive and chemo-therapeutic activities and is under investigation for the treatment of various human cancers. However, the clinical application of curcumin has been significantly limited by its instability and poor metabolic property. Although a number of synthetic modifications of curcumin have been studied intensively in order to develop a molecule with enhanced bioactivities, few synthetic studies were done for the improvement of pharmacokinetic profiles. In the present study, a series of mono-carbonyl analogues of curcumin were designed and synthesized by deleting the reactive β-diketone moiety, which was considered to be responsible for the pharmacokinetic limitation of curcumin. The results of the in vitro stability studies and in vivo pharmacokinetic studies indicated that the stability of these mono-carbonyl analogues was greatly enhanced in vitro and their pharmacokinetic profiles were also significantly improved in vivo. Furthermore, the cytotoxic activities of mono-carbonyl analogues were evaluated in seven different tumor cell lines by MTT assay and the structure–activity relation (SAR) was discussed and concluded. The results suggest that the five-carbon linker-containing analogues of curcumin may be favorable for the curcumin-based drug development both pharmacokinetically and pharmacologically. 相似文献
974.
蚂蚁是分布广泛、种类和数量丰富的社会性昆虫.蚂蚁的传统分类学研究存在一定局限性,而分子生物学为蚂蚁的系统学研究提供了新途径.概述了蚂蚁分子系统学在研究内容和技术方法上的研究进展,并对今后的研究做了展望. 相似文献
975.
Ivan F.N. Hung Pierre Chan Sally Leung Fion S.Y. Chan Axel Hsu David But Wai Kay Seto Siu Yin Wong Chi Kuen Chan Qing Gu Teresa S.M. Tong Ting Kin Cheung Kent Man Chu Benjamin C.Y. Wong 《Helicobacter》2009,14(6):505-511
Background: Recent studies have suggested the eradication rate for Helicobacter pylori infection with standard amoxycillin–clarithromycin‐containing triple therapy as first‐line treatment have fallen below 80%. Levofloxacin‐containing triple therapy was proposed as an alternative. The aim of this study is to compare the efficacy and tolerability of the standard 7‐day clarithromycin‐containing triple therapy against the 7‐day levofloxacin‐containing triple therapy, and to assess whether the classical triple therapy is still valid as empirical first‐line treatment for H. pylori infection in Hong Kong. Methods: Three hundred consecutive H. pylori‐positive patients were randomized to receive either 1 week of EAL (esomeprazole 20 mg b.d., amoxycillin 1 g b.d., and levofloxacin 500 mg daily) or EAC (esomeprazole 20 mg b.d., amoxycillin 1 g b.d., and clarithromycin 500 mg b.d.). H. pylori status was rechecked by 13C‐urea breath test 6 weeks after treatment. Patients who failed either of the first‐line eradication therapy were invited to undergo H. pylori susceptibility testing. Results: H. pylori eradication was achieved in 128 of 150 (85.3%) patients in EAL and 139 of 150 (92.7%) patients in EAC groups, respectively (p = .043), for both intention‐to‐treat and per‐protocol analysis. More patients in the clarithromycin‐ than the levofloxacin‐containing therapy group developed side effects from the medication (21.3% vs 13.3%, p = .060). Nine patients (six from the EAL group and three from the EAC group) who failed their corresponding eradication therapy returned for susceptibility testing. All nine isolates were highly resistant to levofloxacin (minimum inhibitory concentration or MIC > 32 μg/mL), whereas only two of the six isolates from the EAL group were resistant to clarithromycin (MIC > 0.5 μg/mL). Conclusions: The standard 7‐day clarithromycin‐containing triple therapy is still valid as the most effective empirical first‐line eradication therapy for H. pylori infection in Hong Kong, as prevalence of primary resistance of H. pylori to amoxycillin and clarithromycin remains low. Patients who failed their empirical first‐line eradication therapy should undergo H. pylori susceptibility testing to guide further treatment. 相似文献
976.
Chu X Tang X Guo L Bao H Zhang S Zhang J Zhu D 《Prostaglandins & other lipid mediators》2009,88(1-2):42-50
Hypoxia initiated pulmonary vasoconstriction is due to the inhibition of voltage-gated K(+) (K(V)) channels. But the mechanism is unclear. We have evidence that hypoxia activates 15-lipoxygenase (15-LOX) in distal pulmonary arteries and increases the formation of 15-hydroxyeicosatetraenoate (15-HETE). 15-HETE-induced pulmonary artery constriction to be through the inhibition of K(V) channels (K(V)1.5, K(V)2.1 and K(V)3.4). However, no direct link among hypoxia, 15-HETE and inhibition of K(V) subtypes is established. Therefore, we investigated whether 15-LOX/15-HETE pathway contributes to the hypoxia-induced down-regulation of K(V) channels. As K(V)1.5 channel is O(2)-sensitive, it was chosen in the initial study. We found that inhibition of 15-LOX suppressed the response of hypoxic pulmonary artery rings to phenylephrine. The expressions of K(V)1.5 channel mRNA and protein was robustly up-regulated in cultured PASMC and pulmonary artery after blocking of 15-LOX by lipoxygenase inhibitors in hypoxia. The 15-LOX blockade also partly rescued the voltage-gated K(+) current (I(K(V))). 15-HETE contributes to the down-regulation of K(V)1.5 channel, inhibition of I(K(V)) and increase of native pulmonary artery tension after hypoxia. Hypoxia inhibits K(V)1.5 channel through 15-LOX/15-HETE pathway. 相似文献
977.
Y.-H. Wang W.-M. He F.-H. Yu L.-L. Zhang Q.-G. Cui Y. Chu & M. Dong 《Plant biology (Stuttgart, Germany)》2009,11(5):694-700
High water availability and mechanical stress can induce opposite responses in plants. In arid areas of Northern China the occurrence of high wind and high water availability tend to be negatively correlated. Since turgor pressure is a determinant of the mechanical stability of annuals, it is hypothesised that the effects of mechanical perturbation (MP) on annuals may depend on soil water availability. To test this proposal, we conducted an experiment in which a pioneering annual Corispermum mongolicum was subjected to two levels of MP and water supply, and then determined its growth and mechanical traits. Brushing had no effect on plant height and total biomass, but stimulated leaf and branch production. Water supply affected plant height, basal diameter, total biomass and stem rigidity, but not leaf and branch number, root/shoot ratio or flexibility. With high water availability, brushing stimulated the production of stiffer stems (thicker and with a higher Young's modulus) and more roots relative to shoot mass, but with low water availability MP induced the opposite response. This shows that both the degree and direction of plant responses to MP depend on the presence of other factors. We discuss how the interactive effects of MP and water availability on growth and mechanical properties may help C. mongolicum to establish in windy and arid environments. 相似文献
978.
摘要:【目的】肺炎克雷伯菌(K.pn)与宿主细胞的粘附是致病的首要条件,粘附过程主要通过菌毛粘附素MrkD蛋白介导。为了进一步分析MrkD蛋白与宿主细胞间的粘附机制,进一步确定MrkD蛋白的粘附阻断作用。【方法】构建肺炎克雷伯菌菌毛粘附素融合蛋白原核表达质粒pGEX-4T-mrkD,转入大肠杆菌BL21,优化诱导表达条件,表达产物经亲和层析纯化、凝血酶切除融合蛋白GST标签后,进行SDS-PAGE和Western blot鉴定。激光共聚焦显微镜定位MrkD蛋白在宿主细胞上的结合部位;通过粘附活性试验与粘附动力学实验研究了MrkD蛋白的生物活性。【结果】实验得到了分子量为35 kDa的MrkD蛋白,定位了MrkD蛋白在宿主细胞上的结合部位,并证明了MrkD蛋白可以显著影响肺炎克雷伯菌对宿主细胞的粘附力。【结论】本试验首次证实了MrkD蛋白的粘附阻断作用并观察到了其与宿主细胞的作用位点,为研究肺炎克雷伯菌的致病机制,寻找粘附素功能表位奠定了基础。 相似文献
979.
Hung-Kuan Tang Hsiang-Yun Tang Yue-Ru Chu Chin-Hang Shu 《Archives of biochemistry and biophysics》2009,485(2):120-3414
Dipetidyl peptidase 9 (DPP9) is a prolyl dipeptidase preferentially cleaving the peptide bond after the penultimate proline residue. The biological function of DPP9 is unknown. In this study, we have significantly improved the yield using Strep·Tactin® purification system and characterized the biochemical property of DPP9. Moreover, the dimer interaction mode was investigated by introducing a mutation (F842A) at the dimer interface, which abolished the enzymatic activity without disrupting its quaternary structure. Furthermore, DPP9 was found ubiquitously expressed in fibroblasts, epithelial, and blood cells. Surprisingly, contrary to previous report, we found that the expression levels of DPP8 and DPP9 did not change upon the activation of the PBMC or Jurkat cells. These results indicate that the biochemical property of DPP9 is very similar to that of DPP8, its homologous protease. DPP9 and DPP8 are likely redundant proteins carrying out overlapping functions in vivo. 相似文献
980.
Maria Teresa Landi Nilanjan Chatterjee Lynn R. Goldin Melissa Rotunno Kevin Jacobs Meredith Yeager Qizhai Li Dario Consonni Sholom Wacholder Ryan Diver Jarmo Virtamo Zhaoming Wang Kimberly F. Doheny Cathy Laurie Rayjean Hung James D. McKay John McLaughlin Ming-Sound Tsao Yufei Wang Lars Vatten Egil Arnesen Christine Bouchard Tonu Vooder Kristian Välk Chu Chen Patrick Sulem Thorunn Rafnar Wiebke Sauter Heike Bickeböller Jenny Chang-Claude Kari Stefansson Christopher I. Amos Sharon A. Savage Margaret A. Tucker Neil E. Caporaso 《American journal of human genetics》2009,85(5):679-74
Three genetic loci for lung cancer risk have been identified by genome-wide association studies (GWAS), but inherited susceptibility to specific histologic types of lung cancer is not well established. We conducted a GWAS of lung cancer and its major histologic types, genotyping 515,922 single-nucleotide polymorphisms (SNPs) in 5739 lung cancer cases and 5848 controls from one population-based case-control study and three cohort studies. Results were combined with summary data from ten additional studies, for a total of 13,300 cases and 19,666 controls of European descent. Four studies also provided histology data for replication, resulting in 3333 adenocarcinomas (AD), 2589 squamous cell carcinomas (SQ), and 1418 small cell carcinomas (SC). In analyses by histology, rs2736100 (TERT), on chromosome 5p15.33, was associated with risk of adenocarcinoma (odds ratio [OR] = 1.23, 95% confidence interval [CI] = 1.13–1.33, p = 3.02 × 10−7), but not with other histologic types (OR = 1.01, p = 0.84 and OR = 1.00, p = 0.93 for SQ and SC, respectively). This finding was confirmed in each replication study and overall meta-analysis (OR = 1.24, 95% CI = 1.17–1.31, p = 3.74 × 10−14 for AD; OR = 0.99, p = 0.69 and OR = 0.97, p = 0.48 for SQ and SC, respectively). Other previously reported association signals on 15q25 and 6p21 were also refined, but no additional loci reached genome-wide significance. In conclusion, a lung cancer GWAS identified a distinct hereditary contribution to adenocarcinoma. 相似文献