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21.
In this study, we characterized a putative peroxidase Prx1 of Candida albicans by: 1) demonstrating the thioredoxin-linked peroxidase activity with purified proteins, 2) examining the sensitivity to several
oxidants and the accumulation of intracellular reactive oxygen species with a null mutant (prx1Δ), a mutant (C69S) with a point mutation at Cys69, and a revertant, and 3) subcelluar localization. Enzymatic assays showed
that Prx1 is a thioredoxin-linked peroxidase which reduces both hydrogen peroxide (H2O2) and tert-butyl hydroperoxide (t-BOOH). Compared with two other strong H2O2 scavenger mutants for TSA1 and CAT1, prx1Δ and C69S were less sensitive to H2O2, menadione and diamide at all concentrations tested, but were more sensitive to low concentration of t-BOOH. Intracellular reactive oxygen species accumulated in prx1Δ and C69S cells treated with t-BOOH but not H2O2. These results suggest that peroxidase activity of Prx1 is specified to t-BOOH in cells. In both biochemical and physiological cases, the evolutionarily conserved Cys69 was found to be essential
for the function. Immunocytochemical staining revealed Prx1 is localized in the cytosol of yeast cells, but is translocated
to the nucleus during the hyphal transition, though the significances of this observation are unclear. Our data suggest that
PRX1 has a thioredoxin peroxidase activity reducing both t-BOOH and H2O2, but its cellular function is specified to t-BOOH. 相似文献
22.
Jooyeon Woo Seok-Kyu Kwon Jungyong Nam Seungwon Choi Hideto Takahashi Dilja Krueger Joohyun Park Yeunkum Lee Jin Young Bae Dongmin Lee Jaewon Ko Hyun Kim Myoung-Hwan Kim Yong Chul Bae Sunghoe Chang Ann Marie Craig Eunjoon Kim 《The Journal of cell biology》2013,201(6):929-944
Synaptic adhesion molecules regulate diverse aspects of synapse formation and maintenance. Many known synaptic adhesion molecules localize at excitatory synapses, whereas relatively little is known about inhibitory synaptic adhesion molecules. Here we report that IgSF9b is a novel, brain-specific, homophilic adhesion molecule that is strongly expressed in GABAergic interneurons. IgSF9b was preferentially localized at inhibitory synapses in cultured rat hippocampal and cortical interneurons and was required for the development of inhibitory synapses onto interneurons. IgSF9b formed a subsynaptic domain distinct from the GABAA receptor– and gephyrin-containing domain, as indicated by super-resolution imaging. IgSF9b was linked to neuroligin 2, an inhibitory synaptic adhesion molecule coupled to gephyrin, via the multi-PDZ protein S-SCAM. IgSF9b and neuroligin 2 could reciprocally cluster each other. These results suggest a novel mode of inhibitory synaptic organization in which two subsynaptic domains, one containing IgSF9b for synaptic adhesion and the other containing gephyrin and GABAA receptors for synaptic transmission, are interconnected through S-SCAM and neuroligin 2. 相似文献
23.
24.
Min-Ji Kim Soo Han Bae Jae-Chan Ryu Younghee Kwon Ji-Hwan Oh Jeongho Kwon 《Autophagy》2016,12(8):1272-1291
Proper regulation of mitophagy for mitochondrial homeostasis is important in various inflammatory diseases. However, the precise mechanisms by which mitophagy is activated to regulate inflammatory responses remain largely unknown. The NLRP3 (NLR family, pyrin domain containing 3) inflammasome serves as a platform that triggers the activation of CASP1 (caspase 1) and secretion of proinflammatory cytokines. Here, we demonstrate that SESN2 (sestrin 2), known as stress-inducible protein, suppresses prolonged NLRP3 inflammasome activation by clearance of damaged mitochondria through inducing mitophagy in macrophages. SESN2 plays a dual role in inducing mitophagy in response to inflammasome activation. First, SESN2 induces “mitochondrial priming” by marking mitochondria for recognition by the autophagic machinery. For mitochondrial preparing, SESN2 facilitates the perinuclear-clustering of mitochondria by mediating aggregation of SQSTM1 (sequestosome 1) and its binding to lysine 63 (Lys63)-linked ubiquitins on the mitochondrial surface. Second, SESN2 activates the specific autophagic machinery for degradation of primed mitochondria via an increase of ULK1 (unc-51 like kinase 1) protein levels. Moreover, increased SESN2 expression by extended LPS (lipopolysaccharide) stimulation is mediated by NOS2 (nitric oxide synthase 2, inducible)-mediated NO (nitric oxide) in macrophages. Thus, Sesn2-deficient mice displayed defective mitophagy, which resulted in hyperactivation of inflammasomes and increased mortality in 2 different sepsis models. Our findings define a unique regulatory mechanism of mitophagy activation for immunological homeostasis that protects the host from sepsis. 相似文献
25.
Ji-Hyeon Park Ji Hae Seo Hee-Jun Wee Tam Thuy Lu Vo Eun Ji Lee Hoon Choi Jong-Ho Cha Bum Ju Ahn Min Wook Shin Sung-Jin Bae Kyu-Won Kim 《PloS one》2014,9(8)
Arrest defective 1 (ARD1) is an acetyltransferase that is highly conserved across organisms, from yeasts to humans. The high homology and widespread expression of ARD1 across multiple species and tissues signify that it serves a fundamental role in cells. Human ARD1 (hARD1) has been suggested to be involved in diverse biological processes, and its role in cell proliferation and cancer development has been recently drawing attention. However, the subcellular localization of ARD1 and its relevance to cellular function remain largely unknown. Here, we have demonstrated that hARD1 is imported to the nuclei of proliferating cells, especially during S phase. Nuclear localization signal (NLS)-deleted hARD1 (hARD1ΔN), which can no longer access the nucleus, resulted in cell morphology changes and cellular growth impairment. Notably, hARD1ΔN-expressing cells showed alterations in the cell cycle and the expression levels of cell cycle regulators compared to hARD1 wild-type cells. Furthermore, these effects were rescued when the nuclear import of hARD1 was restored by exogenous NLS. Our results show that hARD1 nuclear translocation mediated by NLS is required for cell cycle progression, thereby contributing to proper cell proliferation. 相似文献
26.
In Kyoon Lyoo Sujung Yoon Perry F. Renshaw Jaeuk Hwang Sujin Bae Gail Musen Jieun E. Kim Nicolas Bolo Hyeonseok S. Jeong Donald C. Simonson Sun Hea Lee Katie Weinger Jiyoung J. Jung Christopher M. Ryan Yera Choi Alan M. Jacobson 《PloS one》2013,8(8)
Type 1 diabetes mellitus (T1DM) usually begins in childhood and adolescence and causes lifelong damage to several major organs including the brain. Despite increasing evidence of T1DM-induced structural deficits in cortical regions implicated in higher cognitive and emotional functions, little is known whether and how the structural connectivity between these regions is altered in the T1DM brain. Using inter-regional covariance of cortical thickness measurements from high-resolution T1-weighted magnetic resonance data, we examined the topological organizations of cortical structural networks in 81 T1DM patients and 38 healthy subjects. We found a relative absence of hierarchically high-level hubs in the prefrontal lobe of T1DM patients, which suggests ineffective top-down control of the prefrontal cortex in T1DM. Furthermore, inter-network connections between the strategic/executive control system and systems subserving other cortical functions including language and mnemonic/emotional processing were also less integrated in T1DM patients than in healthy individuals. The current results provide structural evidence for T1DM-related dysfunctional cortical organization, which specifically underlie the top-down cognitive control of language, memory, and emotion. 相似文献
27.
Basolateral plasma membrane localization of ouabain-sensitive sodium transport sites in the secretory epithelium of the avian salt gland 下载免费PDF全文
The distribution of Na+ pump sites (Na+-K+-ATPase) in the secretory epithelium of the avian salt gland was demonstrated by freeze-dry autoradiographic analysis of [(3)H] ouabain binding sites. Kinetic studies indicated that near saturation of tissue binding sites occurred when slices of salt glands from salt-stressed ducks were exposed to 2.2 μM ouabain (containing 5 μCi/ml [(3)H]ouabain) for 90 min. Washing with label-free Ringer's solution for 90 min extracted only 10% of the inhibitor, an amount which corresponded to ouabain present in the tissue spaces labeled by [(14)C]insulin. Increasing the KCl concentration of the incubation medium reduced the rate of ouabain binding but not the maximal amount bound. In contrast to the low level of ouabain binding to salt glands of ducks maintained on a freshwater regimen, exposure to a salt water diet led to a more than threefold increase in binding within 9-11 days. This increase paralleled the similar increment in Na+-K+-ATPase activity described previously. [(3)H]ouabain binding sites were localized autoradiographically to the folded basolateral plasma membrane of the principal secretory cells. The luminal surfaces of these cells were unlabeled. Mitotically active peripheral cells were also unlabeled. The cell-specific pattern of [(3)H]ouabain binding to principal secretory cells and the membrane-specific localization of binding sites to the nonluminal surfaces of these cells were identical to the distribution of Na+-K+-ATPase as reflected by the cytochemical localization of ouabain-sensitive and K+-dependent nitrophenyl phosphatase activity. The relationship between the nonluminal localization of Na+-K+-ATPase and the possible role of the enzyme n NaCl secretion is considered in the light of physiological data on electrolyte transport in salt glands and other secretory epithelia. 相似文献
28.
As corporate responsibility for environmental management has gained attention, eco‐efficiency has become recognized as an important concept for improving the social performance of the business sector as well as that of the public sector. Improving eco‐efficiency is widely accepted not only as a means of increasing economic value, but also as a means of reducing environmental effects. However, managing for eco‐efficiency should take into consideration the differences among industries, because the impact of eco‐efficiency on financial and social performance varies among industries. To explore this variation, we conducted a cross‐industry analysis of eco‐efficiency based on social performance using data envelopment analysis (DEA). DEA measures relative efficiency and is a useful tool for taking into account the relative importance of industry‐specific characteristics. Using DEA, eco‐efficiency scores were derived based on the ratio of two factors of social performance: (1) value‐added inducing and production‐inducing economic spillover effects and (2) the amount of greenhouse gases emitted and energy used. Then, we identified the relationships between our eco‐efficiency score and financial performance, which is a measure of the firm's stability. The case study is based on 272 firms in 16 industries in South Korea. Results show that firms in product manufacturing and service‐intensive industries tend to have higher eco‐efficiency scores than those in raw material or chemical‐intensive industries. In addition, most of the industries reveal no relationship between traditional financial performance metrics and eco‐efficiency scores. A handful of industries had significant relationships with one or more financial performance metrics; in some cases, these relationships were negative, whereas in others they were positive. Surprisingly, almost all industries have no significant relationships between eco‐efficiency and financial performance. This result implies that government support for policies that reward firms that attempt to be eco‐efficient are needed, or that other nonfinancial metrics that influence eco‐efficiency, such as employment and brand reputation, should be considered. This article is expected to support policy makers as they formulate industry‐specific environmental strategies. 相似文献
29.
Kyeong Min Min Young Gi Bae Jong Seob Lee Young Hee Choi Young Ryun Cha Sung Ho Cho 《Journal of Plant Biology》1997,40(4):234-239
Aminoalcoholphosphotransferase is the enzyme that catalyzes the synthesis of phosphatidylcholine and phosphatidylethanolamine from diacylglycerol using CDP-aminoalcohol such as CDP-choline and CDP-ethanolamine. To determine its cDNA structure from roots of Chinese cabbage,Brassica campestris L. ssp.pekinensis, degenerate primers were designed from the regions showing high amino acid homology between yeastCPT1 and soybeanAAPT1 and used for PCR amplification of Chinese cabbage DNA. Chinese cabbage aminoalcoholphosphotransferase cDNA (AAPT) contains an open reading frame of 1,167 bp coding for a protein of 389 amino acids. It shared 81% identity and 94% similarity with soybeanAAPT1 at the predicted amino acid level. Hydropathy profile analysis suggested that the predicted protein structure of Chinese cabbage aminoalcoholphosphotransferase was very similar to the soybean enzyme, showing an overall hydrophobicity and having the same number of predicted transmembrane domains. Southern analysis indicated that there might be close isoforms of the enzyme.AAPT was expressed equally well in young shoots and roots. 相似文献
30.
Bae GU Kim YK Kwon HK Park JW Lee EK Paek SJ Choi WS Jung ID Lee HY Cho EJ Lee HW Han JW 《Experimental cell research》2004,300(2):476-484
We previously reported that hydrogen peroxide (H2O2) mediates mitogen activation of ribosomal protein S6 kinase 1 (S6K1) which plays an important role in cell proliferation and growth. In this study, we investigated a possible role of H2O2 as a molecular linker in Rac1 activation of S6K1. Overexpression of recombinant catalase in NIH-3T3 cells led to the drastic inhibition of H2O2 production by PDGF, which was accompanied by a decrease in S6K1 activity. Similarly, PDGF activation of S6K1 was significantly inhibited by transient transfection or stable transfection of the cells with a dominant-negative Rac1 (Rac1N17), while overexpression of constitutively active Rac1 (Rac1V12) in the cells led to an increase in basal activity of S6K1. In addition, stable transfection of Rat2 cells with Rac1N17 dramatically attenuated the H2O2 production by PDGF as compared with that in the control cells. In contrast, Rat2 cells stably transfected with Rac1V12 produced high level of H2O2 in the absence of PDGF, comparable to that in the control cells stimulated with PDGF. More importantly, elimination of H2O2 produced in Rat2 cells overexpressing Rac1V12 inhibited the Rac1V12 activation of S6K1, indicating the possible role of H2O2 as a mediator in the activation of S6K1 by Rac1. However, H2O2 could be also produced via other pathway, which is independent of Rac1 or PI3K, because in Rat2 cells stably transfected with Rac1N17, H2O2 could be produced by arsenite, which has been shown to be a stimulator of H2O2 production. Taken together, these results suggest that H2O2 plays a pivotal role as a mediator in Rac1 activation of S6K1. 相似文献