Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
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Heart tissue contains appreciable amounts of fatty acid-binding protein (FABP). FABP is thought to play a crucial role in the transport of fatty acids from the cellular membrane to the intracellular site of oxidation and also, in case of endothelial cells, in the transfer of fatty acids from the vascular to the interstitial compartment through the endothelial cytoplasm. The present study was designed to delineate a possible quantitative relationship between the capacity of different cell types in the heart to oxidize fatty acids and the presence of FABP. Palmitate oxidation capacity, measured in homogenates of cells isolated from adult rat hearts, was 2 nmol/min per mg tissue protein in freshly isolated cardiomyocytes (CMC), but only 0.09 and 0.31 nmol/min per mg tissue protein in cultivated endothelial (CEC) and fibroblast-like cells (CFLC), respectively. Palmitate oxidation rates were closely related to the cytochrome C oxidase activity and, hence, to the mitochondrial density in the cells under investigation. In CMC the content of cytosolic H-FABP (H-FABPc) was about 4.5 micrograms/mg tissue protein. However, in CEC and CFLC the FABP content was less than 0.01 and 0.004 micrograms/mg tissue protein, respectively, corresponding to at maximum 0.2% of the FABP content of CMC. These findings indicate a marked difference between CMC and non-myocytal cells in the heart regarding their capacity to oxidize fatty acids, and a marked disproportion between the fatty acid oxidation capacity and immunochemically determined FABP content in both CEC and CFLC. The functional implication of these observations remains to be elucidated.
Mol Cell Biochem
PMID:Fatty acid oxidation capacity and fatty acid-binding protein content of different cell types isolated from rat heart. 217 72

Catecholamines may influence vascular smooth muscle cell (SMC) growth and vascular hypertrophic diseases. We previously demonstrated that stimulation of alpha1-adrenoceptors (AR) causes hypertrophy of vascular SMCs in vitro and in situ. Here, we used adult rat aorta SMCs that express alpha1D- and alpha1B-ARs (but not alpha1A-ARs) in vitro to examine the mechanisms and alpha1-AR subtypes involved. Norepinephrine (NE) increased protein synthesis and content in a time- and dose-dependent manner. To identify the responsible alpha1-AR subtype, we first documented the selectivity of two alpha1-AR subtype antagonists, BMY 7378 (alpha1D-AR antagonist) and chloroethylclonidine (CEC; alpha1B-AR antagonist), using Rat-1 fibroblasts stably transfected with the three different rodent alpha1-AR cDNAs. NE dose-dependently increased protein synthesis in each cell line. In alpha1D fibroblasts, BMY 7378 inhibited growth and protected alpha1D-ARs from CEC alkylation while having little blocking or protecting effect on the growth induced by stimulation of fibroblasts that express alpha1A- or alpha1B-ARs. In rat aorta SMCs, pretreatment with CEC in the presence of BMY 7378 to protect alpha1D-ARs had no effect on NE-induced protein synthesis. BMY 7378 inhibited the SMC growth response with a pKb of 8.4. NE caused rapid and transient p42-p44 mitogen-activated protein kinase (MAPK) activation that was alpha1D-AR dependent. Furthermore, NE caused tyrosine phosphorylation of multiple cellular proteins, phosphorylation of Raf-1, and stimulation of c-fos mRNA expression in aorta SMCs. The selective MAPK kinase inhibitor PD 98059 inhibited NE-induced protein synthesis and MAPK activation with IC50 values of 2.3 and 1.6 microM, respectively. These data demonstrate that SMC growth induced by NE is mediated by alpha1D-ARs that couple to activation of the MAPK cascade.
Mol Pharmacol 1997 May
PMID:Alpha1D-adrenergic receptors and mitogen-activated protein kinase mediate increased protein synthesis by arterial smooth muscle. 914 14

Involvement of receptor subtypes in the alpha 1-adrenoceptor mediated activation of Na/K/2Cl-cotransport and K+ channels was studied in isolated perfused spontaneously beating rat hearts stimulated by phenylephrine (30 mumol/l) in the presence of a beta-adrenoceptor antagonist (1 mumol/l timolol). The effects of alpha 1-adrenoceptor stimulation on K+ translocation mechanisms were studied by measuring the efflux of 86Rb+ (a potassium analogue). The effects of 50 mumol/l bumetanide (Na/K/2Cl-cotransport inhibitor) and 0.1-0.3 mmol/l 4-aminopyridine (inhibitor of K+ channels) were studied in the presence of alpha 1-adrenoceptor subtype selective antagonists. Bumetanide reduced the alpha 1-adrenoceptor mediated increase in 86Rb+ efflux by 53 +/- 16.4% (n = 14, P < 0.001) in hearts pretreated with the preferentially alpha 1B-adrenoceptor antagonist chloroethylclonidine (CEC, 10 mumol/l), and by 35 +/- 7.3% (n = 15, P < 0.001) in the presence of the preferentially alpha 1D-adrenoceptor antagonist BMY 7378 (1 mumol/l). In the presence of the preferentially alpha 1A-adrenoceptor antagonist 5-methylurapidil (10 mumol/l), however, bumetanide had no effect on the response to phenylephrine. 4-Aminopyridine reduced the phenylephrine stimulated 86Rb+ efflux in the presence of 5-methylurapidil, but the effect of the K(+)-channel blocker was eliminated in CEC treated hearts. Thus the effects of the two translocation inhibitors were influenced differently by the two subtype selective antagonists, showing that alpha 1-adrenoceptor stimulation activates a bumetanide sensitive Na/K/2Cl-cotransport mechanism in the rat heart mainly through the alpha 1A-receptor subtype while the 4-aminopyridine sensitive K+ channels, are mainly activated by the alpha 1B-adrenoceptor subtype.
Res Commun Mol Pathol Pharmacol 1997 Jun
PMID:Alpha 1-adrenoceptor mediated activation of Na/K/2Cl cotransport and K+ channels in the rat heart involves different receptor subtypes. 926 92

The third helix of the homeodomain of the Antennapedia homeoprotein can translocate through the cell membrane into the nucleus and can be used as an intracellular vehicle for the delivery of oligopeptides and oligonucleotides. A 16-amino acid-long peptide fragment, called penetratin, is internalized by the cells in a specific, non-receptor-mediated manner. For a better understanding of the mechanism of the transfer, penetratin and two analogs were synthesized:The conformation of penetratin peptides 1-3 was examined in both extracellular matrix-mimetic and membrane-mimetic environments. (1)H-NMR and CD spectroscopic measurements were performed in mixtures of TFE/water with different ratios. Peptides 1-3 were labeled by reacting their N-terminal free amino group with fluorescein isothiocyanate (FITC). Membrane translocation of the labelled peptides was studied with cell cultures [WEHI 164 murine fibrosarcoma cells (WC/1); chicken fibroblast cells (CEC-32); chicken monocytic cells (HD-11); human fibroblast (SV 80) and human monocytic cells (MonoMac-6)]. Confocal laser scanning microscopy and flow cytometry assay were used to study membrane translocation. Amphiphilicity was calculated for each peptide. In our experiments all the penetratin peptides penetrated into the cells. Helical conformation and membrane translocation ability showed little correlation: substitution of the two Trp with Phe increased the stability of helical conformation but decreased membrane translocation activity. The results of fluorescence microscopy and flow cytometry show that penetratin can be translocated into the cells by two mechanisms: endocytosis and direct transport through the cell membrane.
J Mol Recognit
PMID:Membrane translocation of penetratin and its derivatives in different cell lines. 1452 40

In this paper, a series of organoclays were prepared from montmorillonites with different CEC and surfactants with different alkyl chain numbers and chain length. Then, FTIR spectroscopy using ATR, DRIFT and KBr pressed disk techniques was used to characterize the local environments of surfactant and host clays in various surfactants modified montmorillonites under wet and dry states. The present study demonstrates that the alkyl chain length and chain number have significant influences on the local environment of the intercalated surfactants. Also, this study indicates that the surface property of the resulting organoclays is affected by the loading and configuration of the intercalated surfactants. In wet state, more gauche conformers are introduced into the alkyl chains in the organoclays with low surfactant loading, evidenced by the shift of CH(2) vibration to higher frequency. Meanwhile, in the case of the organo-montmorillonites with high surfactant loading, the interaction between the surfactant and silicate surface results in a re-arrangement of SiO(4) tetrahedral sheets and a splitting of Si-O stretching vibration. The KBr pressed disk technique is suitable to probe the conformational ordering of the confined amine chains and the reflectance spectroscopy with ATR and/or DRIFT technique is more suitable to probe the water in organoclays. These findings are of high importance to the preparation of organoclays with proper surfactants and investigation of the microstructure of the resulting organoclays using suitable techniques.
Spectrochim Acta A Mol Biomol Spectrosc 2010 Jul
PMID:Infrared investigation of organo-montmorillonites prepared from different surfactants. 2036 64

Ocular angiogenic diseases, such as proliferative diabetic retinopathy and neovascular age-related macular degeneration, are associated with severe loss of vision. These pathologies originate from different vascular beds, retinal and choroidal microvasculatures, respectively. The activation of endothelial cells (EC) plays pivotal roles in angiogenesis, often triggered by oxygen deficiency. Hypoxia-inducible factors in ECs mediate the transcription of multiple angiogenic genes, including the canonical vascular endothelial growth factors. ECs show notable heterogeneity in function, structure, and disease, therefore the understanding of retinal/choroidal ECs (REC; CEC) biochemical and molecular responses to hypoxia may offer key insights into tissue-specific vascular targeting treatments. The aim of this review is to discuss the differences spanning between REC and CEC, with focus on their response to hypoxia, which could provide innovative and sustainable strategies for site specific targeting of ocular neovascularization.
Int J Mol Sci 2018 Dec 03
PMID:The Different Facades of Retinal and Choroidal Endothelial Cells in Response to Hypoxia. 3051 85