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Adenine derivatives and auxin-related compounds, 2,4-dichlorophenoxyaceticacid (2,4-D) and 2,3,5-triiodobenzoic acid (TIBA), did not inhibitthe transport systems for succinate or malate into mitochondria.In iso-osmotic KC1 medium, some of these compounds increasedion fluxes moderately. TIBA and 2,4-D inhibited the mitochondrialshrinkage induced by the substrates. In contrast, adenine derivativesinhibited only the shrinkage induced by the substrate whoseoxidation they were able to block specifically. (Received February 18, 1987; Accepted June 29, 1987) 相似文献
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Elizabeth Storer Scholl Antonella Pirone Daniel H Cox R Keith Duncan Michele H Jacob 《Channels (Austin, Tex.)》2014,8(1):62-75
Small conductance Ca2+-sensitive potassium (SK2) channels are voltage-independent, Ca2+-activated ion channels that conduct potassium cations and thereby modulate the intrinsic excitability and synaptic transmission of neurons and sensory hair cells. In the cochlea, SK2 channels are functionally coupled to the highly Ca2+ permeant α9/10-nicotinic acetylcholine receptors (nAChRs) at olivocochlear postsynaptic sites. SK2 activation leads to outer hair cell hyperpolarization and frequency-selective suppression of afferent sound transmission. These inhibitory responses are essential for normal regulation of sound sensitivity, frequency selectivity, and suppression of background noise. However, little is known about the molecular interactions of these key functional channels. Here we show that SK2 channels co-precipitate with α9/10-nAChRs and with the actin-binding protein α-actinin-1. SK2 alternative splicing, resulting in a 3 amino acid insertion in the intracellular 3′ terminus, modulates these interactions. Further, relative abundance of the SK2 splice variants changes during developmental stages of synapse maturation in both the avian cochlea and the mammalian forebrain. Using heterologous cell expression to separately study the 2 distinct isoforms, we show that the variants differ in protein interactions and surface expression levels, and that Ca2+ and Ca2+-bound calmodulin differentially regulate their protein interactions. Our findings suggest that the SK2 isoforms may be distinctly modulated by activity-induced Ca2+ influx. Alternative splicing of SK2 may serve as a novel mechanism to differentially regulate the maturation and function of olivocochlear and neuronal synapses. 相似文献
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Plant chloroplasts are not only the main cellular location for storage of elemental iron (Fe), but also the main site for Fe, which is incorporated into chlorophyll, haem and the photosynthetic machinery. How plants measure internal Fe levels is unknown. We describe here a new Fe‐dependent response, a change in the period of the circadian clock. In Arabidopsis, the period lengthens when Fe becomes limiting, and gradually shortens as external Fe levels increase. Etiolated seedlings or light‐grown plants treated with plastid translation inhibitors do not respond to changes in Fe supply, pointing to developed chloroplasts as central hubs for circadian Fe sensing. Phytochrome‐deficient mutants maintain a short period even under Fe deficiency, stressing the role of early light signalling in coupling the clock to Fe responses. Further mutant and pharmacological analyses suggest that known players in plastid‐to‐nucleus signalling do not directly participate in Fe sensing. We propose that the sensor governing circadian Fe responses defines a new retrograde pathway that involves a plastid‐encoded protein that depends on phytochromes and the functional state of chloroplasts. 相似文献
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Vincenzo Pavone Angelina Lombardi Michele Saviano Benedetto Di Blasio Flavia Nastri Roberto Fattorusso Ornella Maglio Carla Isernia 《Biopolymers》1994,34(11):1505-1515
In the present paper we describe the synthesis, purification, single crystal x-ray analysis, and solution structural characterization by nmr spectroscopy, combined with restrained molecular dynamic simulations, of the cyclic hexapeptide cyclo-(Pro-Phe-β-Ala-Phe-Phe-β-Ala). The peptide was synthesized by classical solution methods and the cyclization of the free hexapeptide was accomplished in good yields in diluted methylenechloride solution using N, N-dicyclohexyl-carbodiimide. The compound crystallizes in the monoclinic space group P21 from methanol/ethyl acetate. The molecule adopts in the solid state a conformation characterized by cis β-Ala6-Pro1 peptide bond. The α-amino acid residues are at the corner positions of turned structures. The Pro1-Phe2 segment is incorporated in a pseudo type I β-turn, while Phe4-Phe5 is in a typical type I β-turn. Assignment of all 1H and 13C resonances was achieved by homo- and heteronuclear two-dimensional techniques in dimethylsulfoxide (DMSO) solutions. The conformational analysis was based on inter-proton distances derived from rotating frame nuclear Overhauser effect spectroscopy spectra and homonuclear coupling constants. Restrained molecular dynamic simulation in vacuo was also performed to built refined molecular models. The molecule is present in DMSO solution as two slowly interconverting conformers, characterized by a cis-tran isomerism around the β-Ala6-Pro1 peptide bond. This work confirms our expectations on the low propensity of β-alanyl residues to be positioned at the corners of turned structure. © 1994 John Wiley & Sons, Inc. 相似文献
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Modulation of molecular mechanisms involved in protein synthesis machinery as a new tool for the control of cell proliferation. 总被引:7,自引:0,他引:7
M Caraglia A Budillon G Vitale G Lupoli P Tagliaferri A Abbruzzese 《European journal of biochemistry》2000,267(13):3919-3936
In the past years, the attention of scientists has focused mainly on the study of the genetic information and alterations that regulate eukaryotic cell proliferation and that lead to neoplastic transformation. All therapeutic strategies against cancer are, to date, directed at DNA either with cytotoxic drugs or gene therapy. Little or no interest has been aroused by protein synthesis mechanisms. However, an increasing body of data is emerging about the involvement of translational processes and factors in control of cell proliferation, indicating that protein synthesis can be an additional target for anticancer strategies. In this paper we review the novel insights on the biochemical and molecular events leading to protein biosynthesis and we describe their involvement in cell proliferation and tumorigenesis. A possible mechanistic explanation is given by the interactions that occur between protein synthesis machinery and the proliferative signal transduction pathways and that are therefore suitable targets for indirect modulation of protein synthesis. We briefly describe the molecular tools used to block protein synthesis and the attempts made at increasing their efficacy. Finally, we propose a new multimodal strategy against cancer based on the simultaneous intervention on protein synthesis and signal transduction. 相似文献