Peroxisome proliferator-activated receptors (PPARs) are key players in lipid and glucose metabolism and are implicated in metabolic disorders predisposing to atherosclerosis, such as dyslipidaemia and diabetes. Whereas PPARgamma promotes lipid storage by regulating adipocyte differentiation, PPARalpha stimulates the beta-oxidative degradation of fatty acids. PPARalpha-deficient mice show a prolonged response to inflammatory stimuli, suggesting that PPARalpha is also a modulator of inflammation. Hypolipidaemic fibrate drugs are PPARalpha ligands that inhibit the progressive formation of atherosclerotic lesions, which involves chronic inflammatory processes, even in the absence of their atherogenic lipoprotein-lowering effect. Here we show that PPARalpha is expressed in human aortic smooth-muscle cells, which participate in plaque formation and post-angioplasty re-stenosis. In these smooth-muscle cells, we find that PPARalpha ligands, and not PPARgamma ligands, inhibit interleukin-1-induced production of interleukin-6 and prostaglandin and expression of cyclooxygenase-2. This inhibition of cyclooxygenase-2 induction occurs transcriptionally as a result of PPARalpha repression of NF-kappaB signalling. In hyperlipidaemic patients, fenofibrate treatment decreases the plasma concentrations of interleukin-6, fibrinogen and C-reactive protein. We conclude that activators of PPARalpha inhibit the inflammatory response of aortic smooth-muscle cells and decrease the concentration of plasma acute-phase proteins, indicating that PPARalpha in the vascular wall may influence the process of atherosclerosis and re-stenosis.

Activation of human aortic smooth-muscle cells is inhibited by PPARα but not by PPARγ activators

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36B4 cDNA used as an estradiol-independent mRNA control is the cDNA for human acidic ribosomal phosphoprotein PO

There are two estrogen receptor (ER) subtypes in fish, ERα and ERβ, and increasing evidence that the ERβ subtype has more than one form. However, there is little information on the characteristics and functional significance of these ERs in adults and during development. Here, we report the cloning and characterization of three functional ER forms, zfERα, zfERβ1, and zfERβ2, in the zebrafish. The percentages of identity between these receptors suggest the existence of three distinct genes. Each cDNA encoded a protein that specifically bound estradiol with a dissociation constant ranging from 0.4 nM (zfERβ2) to 0.75 nM (zfERα and zfERβ1). In transiently transfected cells, all three forms were able to induce, in a dose-dependent manner, the expression of a reporter gene driven by a consensus estrogen responsive element; zfERβ2 was slightly more sensitive than zfERα and zfERβ1. Tissue distribution pattern, analyzed by reverse transcription polymerase chain reaction, showed that the three zfER mRNAs ...

https://bioone.org/journals/biology-of-reproduction/volume-66/issue-6/biolreprod66.6.1881/Molecular-Characterization-of-Three-Estrogen-Receptor-Forms-in-Zebrafish/10.1095/biolreprod66.6.1881.pdf

Molecular Characterization of Three Estrogen Receptor Forms in Zebrafish: Binding Characteristics, Transactivation Properties, and Tissue Distributions

Guinea pig eotaxin is a recently described member of the Cys-Cys family of chemokines and is involved in a guinea pig model of asthma. To determine whether eotaxin is a distinctive member of this family and to understand its physiologic role, we have cloned the mouse eotaxin gene and determined its structure and aspects of its biologic function. The sequence relationship between the mouse and guinea pig genes indicates that eotaxin is indeed a distinct member of the chemokine family. Moreover, murine eotaxin maps to a region of mouse chromosome 11 that encodes other Cys-Cys chemokines. In addition, recombinant murine eotaxin protein has direct chemoattractant properties for eosinophils. The eotaxin gene is widely (but not ubiquitously) expressed in normal mice and is strongly induced in cultured endothelial cells in response to interferon gamma. Eotaxin is also induced locally in response to the transplantation of interleukin 4-secreting tumor cells, indicating that it likely contributes to the eosinophil recruitment and antitumor effect of interleukin 4. Such responses suggest that eotaxin may be involved in multiple inflammatory states.

https://www.pnas.org/content/pnas/92/19/8960.full.pdf

Murine eotaxin: an eosinophil chemoattractant inducible in endothelial cells and in interleukin 4-induced tumor suppression

Mammalian (rat) ribosomes have 80 proteins; the sequence of amino acids in 75 have been determined. What has been learned of the structure of the rat ribosomal proteins is reviewed with particular ...

Structure and evolution of mammalian ribosomal proteins

cDNA clones encoding three antigenically related human ribosomal phosphoproteins (P-proteins) P0, P1, and P2 were isolated and sequenced. P1 and P2 are analogous to Escherichia coli ribosomal protein L7/L12, and P0 is likely to be an analog of L10. The three proteins have a nearly identical carboxy-terminal 17-amino-acid sequence (KEESEESD(D/E)DMGFGLFD-COOH) that is the basis of their immunological cross-reactivity. The identities of the P1 and P2 cDNAs were confirmed by the strong similarities of their encoded amino acid sequences to published primary structures of the homologous rat, brine shrimp, and Saccharomyces cerevisiae proteins. The P0 cDNA was initially identified by translation of hybrid-selected mRNA and immunoprecipitation of the products. To demonstrate that the coding sequences are full length, the P0, P1, and P2 cDNAs were transcribed in vitro by bacteriophage T7 RNA polymerase and the resulting mRNAs were translated in vitro. The synthetic P0, P1, and P2 proteins were serologically and electrophoretically identical to P-proteins extracted from HeLa cells. These synthetic P-proteins were incorporated into 60S but not 40S ribosomes and also assembled into a complex similar to that described for E. coli L7/L12 and L10.

B E Rich

Papers

Human acidic ribosomal phosphoproteins P0, P1, and P2: analysis of cDNA clones, in vitro synthesis, and assembly.