排序方式: 共有9条查询结果,搜索用时 203 毫秒
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Lixian Chen Tianhao Zhou Nan Wu April OBrien Julie Venter Ludovica Ceci Konstantina Kyritsi Paolo Onori Eugenio Gaudio Amelia Sybenga Linglin Xie Chaodong Wu Luca Fabris Pietro Invernizzi David Zawieja Suthat Liangpunsakul Fanyin Meng Heather Francis Shannon Glaser 《生物化学与生物物理学报:疾病的分子基础》2019,1865(6):1525-1539
Melatonin, a neuroendocrine hormone synthesized by the pineal gland and cholangiocytes, decreases biliary hyperplasia and liver fibrosis during cholestasis-induced biliary injury via melatonin-dependent autocrine signaling through increased biliary arylalkylamine N-acetyltransferase (AANAT) expression and melatonin secretion, downregulation of miR-200b and specific circadian clock genes. Melatonin synthesis is decreased by pinealectomy (PINX) or chronic exposure to light. We evaluated the effect of PINX or prolonged light exposure on melatonin-dependent modulation of biliary damage/ductular reaction/liver fibrosis. Studies were performed in male rats with/without BDL for 1 week with 12:12 h dark/light cycles, continuous light or after 1 week of PINX. The expression of AANAT and melatonin levels in serum and cholangiocyte supernatant were increased in BDL rats, while decreased in BDL rats following PINX or continuous light exposure. BDL-induced increase in serum chemistry, ductular reaction, liver fibrosis, inflammation, angiogenesis and ROS generation were significantly enhanced by PINX or light exposure. Concomitant with enhanced liver fibrosis, we observed increased biliary senescence and enhanced clock genes and miR-200b expression in total liver and cholangiocytes. In vitro, the expression of AANAT, clock genes and miR-200b was increased in PSC human cholangiocyte cell lines (hPSCL). The proliferation and activation of HHStecs (human hepatic stellate cell lines) were increased after stimulating with BDL cholangiocyte supernatant and further enhanced when stimulated with BDL rats following PINX or continuous light exposure cholangiocyte supernatant via intracellular ROS generation. Conclusion: Melatonin plays an important role in the protection of liver against cholestasis-induced damage and ductular reaction. 相似文献
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Flavoproteins can dramatically adjust the thermodynamics and kinetics of electron transfer at their flavin cofactor. A versatile regulatory tool is proton transfer. Here, we demonstrate the significance of proton-coupled electron transfer to redox tuning and semiquinone (sq) stability in photolyases (PLs) and cryptochromes (CRYs). These light-responsive proteins share homologous overall architectures and FAD-binding pockets, yet they have evolved divergent functions that include DNA repair, photomorphogenesis, regulation of circadian rhythm, and magnetoreception. We report the first measurement of both FAD redox potentials for cyclobutane pyrimidine dimer PL (CPD-PL, Anacystis nidulans). These values, E(1)(hq/sq) = -140 mV and E(2)(sq/ox) = -219 mV, where hq is FAD hydroquinone and ox is oxidized FAD, establish that the sq is not thermodynamically stabilized (ΔE = E(2) - E(1) = -79 mV). Results with N386D CPD-PL support our earlier hypothesis of a kinetic barrier to sq oxidation associated with proton transfer. Both E(1) and E(2) are upshifted by ~ 100 mV in this mutant; replacing the N5-proximal Asn with Asp decreases the driving force for sq oxidation. However, this Asp alleviates the kinetic barrier, presumably by acting as a proton shuttle, because the sq in N386D CPD-PL oxidizes orders of magnitude more rapidly than wild type. These data clearly reveal, as suggested for plant CRYs, that an N5-proximal Asp can switch on proton transfer and modulate sq reactivity. However, the effect is context-dependent. More generally, we propose that PLs and CRYs tune the properties of their N5-proximal residue to adjust the extent of proton transfer, H-bonding patterns, and changes in protein conformation associated with electron transfer at the flavin. 相似文献
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Cryptochromes are blue-light absorbing photoreceptors found in many organisms where they have been involved in numerous growth,
developmental, and circadian responses. In Arabidopsis thaliana, two cryptochromes, CRY1 and CRY2, mediate several blue-light-dependent responses including hypocotyl growth inhibition.
Our study shows that an increase in the intensity of the ambient magnetic field from 33–44 to 500 μT enhanced growth inhibition
in A. thaliana under blue light, when cryptochromes are the mediating photoreceptor, but not under red light when the mediating receptors
are phytochromes, or in total darkness. Hypocotyl growth of Arabidopsis mutants lacking cryptochromes was unaffected by the increase in magnetic intensity. Additional cryptochrome-dependent responses,
such as blue-light-dependent anthocyanin accumulation and blue-light-dependent degradation of CRY2 protein, were also enhanced
at the higher magnetic intensity. These findings show that higher plants are sensitive to the magnetic field in responses
that are linked to cryptochrome-dependent signaling pathways. Because cryptochromes form radical pairs after photoexcitation,
our results can best be explained by the radical-pair model. Recent evidence indicates that the magnetic compass of birds
involves a radical pair mechanism, and cryptochrome is a likely candidate for the avian magnetoreception molecule. Our findings
thus suggest intriguing parallels in magnetoreception of animals and plants that appear to be based on common physical properties
of photoexcited cryptochromes. 相似文献
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Guoyuan Qi Rui Guo Haoyu Tian Lixia Li Hua Liu Yashi Mi Xuebo Liu 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2018,1863(6):549-562
Scope
Circadian clock plays a principal role in orchestrating our daily physiology and metabolism, and their perturbation can evoke metabolic diseases such as fatty liver and insulin resistance. Nobiletin (NOB) has been demonstrated to possess antitumor and neuroprotective activities. The objective of the current study is to determine potential effects of NOB on modulating the core clock gene Bmal1 regarding ameliorating glucolipid metabolic disorders.Results
Our results revealed that NOB partially reverse the relatively shallow daily oscillations of circadian clock genes and reset phase-shifting circadian rhythms in primary hepatocytes under metabolic disorders conditions. Importantly, NOB was found to be effective at amplifying glucose uptake via stimulating IRS-1/AKT signaling pathway, as well as blunting palmitate-induced lipogenesis in HepG2 cells via modulating AMPK-Sirt1 signaling pathway and key enzymes of de novo lipogenesis in a Bmal1-dependent manner. NOB attenuated palmitate-stimulated excessive secretions of ROS, restored the depletions of mitochondrial membrane potential, which is similar to the recovery in expressions of mitochondrial respiration complex I-IV.Conclusion
This study is the first to provide compelling evidences that NOB prevent cellular glucolipid metabolic imbalance and mitochondrial function in a Bmal1-dependent manner. Overall, NOB may serve as a nutritional preventive strategy in recovering metabolic disorders relevant to circadian clock. 相似文献6.
M A HAIDAR 《The Annals of applied biology》2003,143(1):57-62
Previous studies demonstrated that blue, near far‐red and a mixture of red and far‐red light stimulate, while red light inhibits coiling and prehaustoria development in young excised de‐etiolated dodder seedlings. In this study, evidence was obtained for the involvement of cryptochromes in the mediation of coiling and prehaustoria development in response to blue light. The results indicated that coiling and prehaustoria are affected by the addition of red or far‐red light and therefore are dependent on the state of phytochromes. Results also suggest the occurrence of a synergistic interaction between phytochromes (Pr) and cryptochromes and an antagonistic interaction between phytochromes (Pfr) and cryptochromes in mediating coiling and prehaustoria development. Gabaculine significantly reduced coiling and prehaustoria development under far‐red or a mixture of red and far‐red light but not under blue or a mixture of blue and far‐red light, indicating that cryptochromes are involved in blue‐induced coiling and prehaustoria development. 相似文献
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Cryptochromes are flavin-based photoreceptors occurring throughout the biological kingdom, which regulate growth and development in plants and are involved in the entrainment of circadian rhythms of both plants and animals. A number of recent theoretical works suggest that cryptochromes might also be the receptors responsible for the sensing of the magnetic field of the earth (e.g. in insects, migratory birds, or migratory fish). Cryptochromes undergo forward light-induced reactions involving electron transfer to excited state flavin to generate radical intermediates, which correlate with biological activity. Here, we give evidence of a mechanism for the reverse reaction, namely dark reoxidation of protein-bound flavin in Arabidopsis thaliana cryptochrome (AtCRY1) by molecular oxygen that involves formation of a spin-correlated FADH•–superoxide radical pair. Formation of analogous radical pairs in animal cryptochromes might enable them to function as magnetoreceptors. 相似文献
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Plants possess photoreceptors to perceive light which controls most aspects of their lives. Three photoreceptor families are
well characterized: cryptochromes (crys), phototropins (phots), and phytochromes (phys). Two putative families have been identified
more recently: Zeitlupes (ZTLs) and UV-B photoreceptors (ULI). Using Arabidopsis thaliana and Oryza sativa photoreceptor sequences as references, we have searched for photoreceptor encoding genes in the major phyla of plant kingdom.
For each photoreceptor family, using a phylogenetic tree based on the alignment of conserved amino acid sequences, we have
tried to trace back the evolution and the emergence of the diverse photoreceptor ancestral sequences.
The green alga Chlamydomonas contains one cry and one phot sequence, probably close to the corresponding ancestral sequences, and no phy-related sequence.
The putative UV-B photoreceptors seem to be restricted to the Brassicacae. Except for mosses and ferns, which contain divergent
photoreceptor numbers, the composition of the diverse photoreceptor families is conserved between species. A high conservation
of the residues within domains is observed in each photoreceptor family. The complete phylogenic analysis of the photoreceptor
families in plants has confirmed the existence of crucial evolutionary nodes between the major phyla. For each photoreceptor
class, a major duplication occurred before the separation between Mono- and Eudicotyledons. This allowed postulating on the
putative ancestral function of the photoreceptors.
[Reviewing Editor: Dr. Rudiger Cerff] 相似文献
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