肝细胞核因子4α与肝脏疾病

肝细胞核因子4α(hepatic nuclear factor 4 alpha,HNF4α)属于细胞核受体超家族成员,它在肝脏的发育、肝细胞分化成熟过程中起重要调控作用。HNF4α有阻断肝纤维化、肝硬化、肝癌的疾病进程,改善肝脏功能的作用。另外,HNF4α在肝干细胞移植方面也发挥重要作用,提高肝细胞移植的成功率。本文就HNF4α在肝细胞中的表达、作用及其相关疾病的研究进展做一综述。     

Lipid-lipid and lipid-protein interactions in chromaffin granule membranes: A spin label ESR study

The ESR spectra of six different positional isomers of a stearic acid and three of a phosphatidylcholine spin label have been studied as a function of temperature in chromaffin granule membranes from the bovine adrenal medulla, and in bilayers formed by aqueous dispersion of the extracted membrane lipids. Only minor differences were found between the spectra of the membranes and the extracted lipid, indicating that the major portion of the membrane lipid is organized in a bilayer arrangement which is relatively unperturbed by the presence of the membrane protein. The order parameter profile of the spin label lipid chain motion is less steep over the first half of the chain than over the section toward the terminal methyl end of the chain. This ‘stiffening’ effect is attributed to the high proportion of cholesterol in the membrane and becomes less marked as the temperature is raised. The isotropic hyperfine splitting factors of the various positional isomers display a profile of decreasing polarity as one penetrates further into the interior of the membrane. No marked differences are observed between the effective polarities in the intact membranes and in bilayers of the extracted membrane lipids. The previously observed temperature-induced structural change occurring in the membranes at approx. 35°C was found also in the extracted lipid bilayers, showing this to be a result of lipid-lipid interactions and not lipid-protein interactions in the membrane. A steroid spin label indicated a second temperature-dependent structural change occurring in the lipid bilayers at lower temperatures. This corresponds to the onset of a more rapid rotation about the long axis of the lipid molecules at a temperature of approx. 10°C. The lipid bilayer regions probed by the spin labels used in this study may be involved in the fusion of the chromaffin granule membrane leading to hormone release by exocytosis.     

Flavonoids from Artemisia ludoviciana var. ludoviciana

Nineteen flavonoids were isolated from Artemisia ludoviciana var. ludoviciana, including a new 2′- hydroxy- 6-methoxyflavone, 5,7,2′,4′-tetrahydroxy-6,5′-dimethoxyflavone. The known compounds include quercetagetin 3,6,3′,4′-tetramethyl ether, eupatilin, 5,7-dihydroxy-3,6,8,4′-tetramethoxyflavone, luteolin 3′,4′-dimethyl ether, jaceosidin, 5,7,4′-trihydroxy-3,6-dimethoxyflavone, tricin, hispidulin, chrysoeriol, kaempferol 3-methyl ether, apigenin, axillarin, eupafolin, selagin and luteolin together with three flavones which were previously isolated for the first time from Artemisia frigida: 5,7,4′-trihydroxy-6, 3′,5′-trimethoxyflavone, 5,7,3′-trihydroxy-6,4′,5′-trimethoxyflavone and 5,7,3′,4′-tetrahydroxy-6,5′- dimethoxyflavone.     

细菌的IV型分泌系统

细菌的分泌系统与细菌的生存及致病性密切相关。细菌的分泌系统包括I-VI型,其中,IV型分泌系统是与细菌接合机制有关的一类分泌系统。IV型分泌系统不但可以转运DNA,还可以转运蛋白质及核糖核蛋白复合物等大分子物质,这点区别于其他几种分泌系统。IV型分泌系统介导基因水平转移,通过细菌间接合作用,传递抗性基因和毒力基因,有利于细菌进化;另一方面,IV型分泌系统转运效应蛋白质分子到宿主细胞,参与细菌致病。本文着重从IV型分泌系统几种主要类型的分泌机制等方面对IV型分泌系统进行概述。     

The configuration of the sesquiterpenoid 4-hydroxy-myoporone (athanagrandione)

The conversion of eremoacetal to (?)-1-(furan-3-yl)-4-hydroxy-4,8-dimethylnonane-1,6-dione establishes the configuration of (?)-4-hydroxymyoporone (athanagrandione) as R.     

BACE1 modulates filopodia-like protrusions induced by sodium channel beta4 subunit

Processing of APP by BACE1 plays a crucial role in the pathogenesis of Alzheimer disease (AD). Recently, the voltage-gated sodium channel (Na_v) β4 subunit (β4), an auxiliary subunit of Na_v that is supposed to serve as a cell adhesion molecule, has been identified as a substrate for BACE1. However, the biological consequence of BACE1 processing of β4 remains illusive. Here, we report the biological effects of β4 processing by BACE1. Overexpression of β4 in Neuro2a cells promoted neurite extension and increased the number of F-actin rich filopodia-like protrusions. While coexpression of BACE1 together with β4 further accelerated neurite extension, the number of filopodia-like protrusions was reduced. Overexpression of C-terminal fragment of β4 that was generated by BACE1 (β4-CTF) partially recapitulated the results obtained with BACE1 overexpression. These results suggest that the processing of β4 by BACE1 regulates neurite length and filopodia-like protrusion density in neurons.     

Metallothionein Inducers Protect Against 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Neurotoxicity in Mice

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a drug that induces parkinsonism in human and non-human primates. Free radicals are thought to be involved in its mechanism of action. Recently, the participation of metallothionein as scavenger of free radicals has been proposed. In this work, we studied the effect of metallothionein inducers in MPTP neurotoxic action. Male swiss albino mice were pretreated either with cadmium (1 mg/kg) or dexamethasone (5 mg/kg), two well-known inducers of metallothionein synthesis, and 5 hours later with an MPTP administration (30 mg/kg). Treatment schedule was repeated daily for either 3 or 5 consecutive days. All animals were killed 7 days after the last administration, and striatal dopamine and homovanillic acid contents were analyzed as an end-point of MPTP neurotoxicity. Striatal dopamine content of cadmium plus MPTP-treated animals (3-days) increased by 32%, and 48% (5-days) vs MPTP-alone animals. Dexamethasone plus MPTP-treated group also showed increased dopamine levels 28% (3-days) and 43% (5-days). MPTP treatment reduced striatal metallothionein concentration (49% vs control animals). Dexamethasone and cadmium increased metallothionein concentrations in MPTP-treated groups, by 77% and 82% respectively. Results suggest that metallothionein induction provide a significant resistance factor against the deleterious effect of MPTP.