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101.
Tanaka M Machida Y Nishikawa Y Akagi T Morishima I Hashikawa T Fujisawa T Nukina N 《Biochemistry》2002,41(32):10277-10286
To examine the effects of aggregation-inducing motifs related to neurodegenerative diseases on amyloid formation of host protein, we prepared several chimera myoglobins, in which various aggregation-inducing motifs were inserted. The focused aggregation-inducing motifs included five (R5) or two (R2) oligopeptide repeats in yeast Sup35p, five octapeptide repeats (OPR) in the human prion protein, a nonamyloid beta component (NAC) in alpha-synuclein, and tandem repeats of 50 glutamines (Q50). Circular dichroism and infrared spectroscopies suggested that the OPR, R5, and Q50 motifs formed an antiparallel beta sheet as well as a random coil, whereas the R2 and NAC motifs mainly formed random coils. The OPR, R5, and Q50 mutants, but not the R2 and NAC mutants, readily formed the SDS-resistant aggregates under physiological condition, and electron microscopy revealed that the aggregates contained amyloid fibrils. The destabilization and increase in gyration radius of the OPR, R5, and Q50 mutants correlated with the tendency to form amyloid fibrils. A control mutant bearing a nonamyloidgenic sequence was also moderately destabilized but did not form amyloid fibrils. Therefore, we concluded that the OPR, R5, and Q50 motifs, even in a quite stable protein such as myoglobin, led the host protein to formation of amyloid fibrils under physiological condition. 相似文献
102.
Toshitaka Nakamura Motoyuki Ogawa Kazuki Kojima Saki Takayanagi Shunya Ishihara Kazuki Hattori Isao Naguro Hidenori Ichijo 《EMBO reports》2021,22(5)
Ferroptosis has recently attracted much interest because of its relevance to human diseases such as cancer and ischemia‐reperfusion injury. We have reported that prolonged severe cold stress induces lipid peroxidation‐dependent ferroptosis, but the upstream mechanism remains unknown. Here, using genome‐wide CRISPR screening, we found that a mitochondrial Ca2+ uptake regulator, mitochondrial calcium uptake 1 (MICU1), is required for generating lipid peroxide and subsequent ferroptosis under cold stress. Furthermore, the gatekeeping activity of MICU1 through mitochondrial calcium uniporter (MCU) is suggested to be indispensable for cold stress‐induced ferroptosis. MICU1 is required for mitochondrial Ca2+ increase, hyperpolarization of the mitochondrial membrane potential (MMP), and subsequent lipid peroxidation under cold stress. Collectively, these findings suggest that the MICU1‐dependent mitochondrial Ca2+ homeostasis‐MMP hyperpolarization axis is involved in cold stress‐induced lipid peroxidation and ferroptosis. 相似文献
103.
Apoptosis in the aging process 总被引:2,自引:0,他引:2
Although many hypotheses have been proposed to explain the aging process, the exact mechanisms are not well defined. Recent accumulating evidence indicates that dysregulation of the apoptotic process may be involved in some aging processes; however, it is still debatable how exactly apoptosis is expressed during aging in vivo. In this review, we discuss recent findings related to apoptosis of individual organs during aging and their significance. We demonstrate that aging enhances apoptosis and susceptibility to apoptosis in several types of intact cells. In contrast, in certain genetically damaged, initiated, and preneoplastic cells, aging suppresses these age-associated apoptotic changes. In various cells, apoptosis enhances the elimination of damaged and dysfunctional cells presumably caused by oxidative stress, glycation, and DNA damage. In these cases, the incidence of apoptosis correlates with the level of accumulated injury. It is concluded that apoptosis plays an important role in the aging process and tumorigenesis in vivo probably as an inherent protective mechanism against age-associated tumorigenesis. 相似文献
104.
Koichi Fujisawa Shuji Terai Toshihiko Matsumoto Taro Takami Naoki Yamamoto Hiroshi Nishina Makoto Furutani-Seiki Isao Sakaida 《PloS one》2015,10(6)
Maid is a helix-loop-helix protein that is involved in cell proliferation. In order to further elucidate its physiological functions, we studied Maid activity in two small fish model systems. We found that Maid expression was greatest in zebrafish liver and that it increased following partial hepatectomy. Maid levels were also high in hepatic preneoplastic foci induced by treatment of zebrafish with diethylnitrosamine (DEN), but low in hepatocellular carcinomas (HCC), mixed tumors, and cholangiocarcinomas developing in these animals. In DEN-treated transgenic medaka overexpressing Maid, hepatic BrdU uptake and proliferation were reduced. After successive breedings, Maid transgenic medaka exhibited decreased movement and a higher incidence of abnormal spine curvature, possibly due to the senescence of spinal cord cells. Taken together, our results suggest that Maid levels can influence the progression of liver cancer. In conclusion, we found that Maid is important regulator of hepatocarconogenesis and aging. 相似文献
105.
Numazawa M Nagaoka M Handa W Ogawa Y Matsuoka S 《The Journal of steroid biochemistry and molecular biology》2007,107(3-5):211-219
To gain insight into the mechanistic features for aromatase inactivation by the typical suicide substrates, androsta-1,4-diene-3,17-dione (ADD, 1) and its 6-ene derivative 2, we synthesized 19-substituted (methyl and halogeno) ADD and 1,4,6-triene derivatives 8 and 10 along with 4,6-diene derivatives 9 and tested for their ability to inhibit aromatase in human placental microsomes as well as their ability to serve as a substrate for the enzyme. 19-Methyl-substituted steroids were the most powerful competitive inhibitors of aromatase (Ki: 8.2–40 nM) in each series. Among the 19-substituted inhibitors examined, 19-chloro-ADD and its 6-ene derivatives (7b and 9b) inactivated aromatase in a time-dependent manner in the presence of NADPH in air while the other ones did not. The time-dependent inactivation was blocked by the substrate AD and required NADPH. Only the time-dependent inactivators 7b and 9b in series of 1,4-diene and 1,4,6-triene steroids as well as all of 4,6-diene steroids 9, except for the methyl compound 9a, served as a substrate for aromatase to yield estradiol and/or its 6-ene estradiol with lower conversion rates compared to the corresponding parent steroids 1,4-diene, 1,4,6-triene and 4,6-diene derivatives. The present findings strongly suggest that the aromatase reaction, 19-oxygenation, at least in part, would be involved in the time-dependent inactivation of aromatase by the suicide substrates 1 and 2, where the 19-substitutent would play a critical role in the aromatase reaction probably though steric and electronic reasons. 相似文献
106.
Sachiko Komatsu Ayaka Yaguchi Kouwa Yamashita Masao Nagaoka Mitsuteru Numazawa 《Steroids》2009,74(12):884-889
Inhibition of aromatase is an efficient approach for the prevention and treatment of breast cancer. New 6β,19-bridged steroid analogs of androstenedione, 6β,19-epithio- and 6β,19-methano compounds 11 and 17, were synthesized starting from 19-hydroxyandrostenedione (6) and 19-formylandrost-5-ene-3β,17β-yl diacetate (12), respectively, as aromatase inhibitors. All of the compounds including known steroids 6β,19-epoxyandrostenedione (4) and 6β,19-cycloandrostenedione (5) tested were weak to poor competitive inhibitors of aromatase and, among them, 6β,19-epoxy steroid 4 provided only moderate inhibition (Ki: 2.2 μM). These results show that the 6β,19-bridged groups of the inhibitors interfere with binding in active site of aromatase. 相似文献
107.
Tetsushi?Yonekura Masatoshi?Yoshidome Makoto?Watanabe Yukie?Honda Isao?Ogiwara Takeshi?IzutaEmail author 《Trees - Structure and Function》2004,18(5):581-588
We examined the carry-over effects of ozone (O3) and/or water stress on leaf phenological characteristics and bud frost hardiness of Fagus crenata seedlings. Three-year-old seedlings were exposed to charcoal-filtered air or 60 nl l–1 O3, 7 h a day, from May to October 1999 in naturally-lit growth chambers. Half of the seedlings in each gas treatment received 250 ml of water at 3-day intervals (well-watered treatment), while the rest received 175 ml of water at the same intervals (water-stressed treatment). All the seedlings were moved from the growth chambers to an experimental field on October 1999, and grown until April 2000 under field conditions. The exposure to O3 during the growing season induced early leaf fall and reduction in leaf non-structural carbohydrates concentrations in the early autumn, as well as resulting in late bud break and reduction in the number of leaves per bud in the following spring. However, O3 did not affect bud frost hardiness in the following winter. On the contrary, water stress did not affect leaf phenological characteristics, leaf and bud non-structural carbohydrates concentrations and bud frost hardiness. There were no significant synergistic or antagonistic effects of O3 and water stress on leaf phenological characteristics, concentrations of leaf and bud non-structural carbohydrates and bud frost hardiness of the seedlings. These results show that the carry-over effects of O3 can be found on the phenological characteristics and leaf non-structural carbohydrates concentrations, although there are almost no carry-over effects of water stress on phenological characteristics and winter hardiness of the seedlings. 相似文献
108.
DGGE method for analyzing 16S rDNA of methanogenic archaeal community in paddy field soil 总被引:24,自引:0,他引:24
A denaturing gradient gel electrophoresis (DGGE) method for analyzing 16S rDNA of methanogenic archaeal community in paddy field soil is presented. Five specific primers for 16S rDNA of methanogenic archaea, which were modified from the primers for archaea, were first evaluated by polymerase chain reaction and DGGE using genomic DNAs of 13 pure culture strains of methanogenic archaea. The DGGE analysis was possible with two primer pairs (0348aF-GC and 0691R; 0357F-GC and 0691R) of the five pairs tested although 16S rDNA of some non-methanogenic archaea was amplified with 0348aF-GC and 0691R. These two primer pairs were further evaluated for use in analysis of methanogenic archaeal community in Japanese paddy field soil. Good separation and quality of patterns were obtained in DGGE analysis with both primer pairs. A total of 41 DNA fragments were excised from the DGGE gels and their sequences were determined. All fragments belonged to methanogenic archaea. These results indicate that the procedure of DGGE analysis with the primer pair 0357F-GC and 0691R is suitable for investigating methanogenic archaeal community in paddy field soil. 相似文献
109.
Shenghui Xu Akiko Kojima-Yuasa Hideki Azuma David Opare Kennedy Yotaro Konishi Isao Matsui-Yuasa 《Chemico-biological interactions》2010,185(3):235-240
In a previous study, we showed that (1′S)-acetoxychavicol acetate ((S)-ACA) caused a rapid decrease in glutathione (GSH) levels less than 15 min after exposure. (S)-ACA-induced cell death was reversed by the addition of N-acetylcysteine. In the current study, we investigated the inhibitory activities of 13 derivatives of (S)-ACA on tumor cell viability, intracellular GSH level and GR activity. Correlations were found among a decrease in cell viability, intracellular GSH levels and the activity of GR in Ehrlich ascites tumor cells treated with the various ACA analogues. A test of the 13 derivatives revealed that the structural factors regulating activity were as follows: (1) the para or 1′-position of acetoxyl group (or other acyl group) was essential, (2) the presence of a C2′–C3′ double or triple bond was essential, and (3) the S configuration of the 1′-acetoxyl group was preferable. 相似文献
110.
Shigeru Kumano Masashi Ihira Yasuo Maeda Misako Yamauchi Eiji Matsumoto Isao Matsuda 《Ecological Research》1990,5(2):221-235
Diatom assemblages of sediments obtained from three sites on Kushiro Moor were analyzed to investigate the Holocene sedimentary
history. The results showed that: 1) The Takkobu site was originally at the bottom of the paleo-Kushiro Bay, and after-wards
the paleo-Takkobu Lagoon developed, became sealed off, and changed to a freshwater lake. The succession to peat moor probably
began about 2000 yr B.P. at the Takkobu site. 2) The Tsurui site was originally at the bottom of the paleo-Kushiro Bay, then
changed to the paleo-Kushiro Lagoon and became peat moor as a result of the first Holocene regression, which finished about
3600 yr B.P. The site then returned to a brackish lake again, probably due to the second Holocene transgression between 3600
and 3000 yr B.P., thereafter passing through brackish lake and freshwater lake stages, and eventually becaming peat moor at
about 2000 yr B.P., 3) At the Chuo site, the second paleo-Kushiro Bay developed again as a result of the second Holocene transgression,
which finished about 3000 yr B.P. Thereafter, brackish or freshwater lakes, rivers, and then peat moor developed in the central
area of Kushiro Moor. 4) The second marine diatom zone (MD2 Zone), which indicates the second Holocene transgression, complete by about 3000 yr B.P., is detected only at the Chuo site
in the central area of Kushiro Moor. 相似文献