Disease relevance of BRB

• Here, the efficient heterologous production of human ANG in Escherichia coli was achieved by replacing two sequences of rare codons with codons favored by E. coli [1].
• Hypoxia decreases plasma aldosterone in vivo without a decrease in PRA, angiotensin II (ANG II), ACTH, or cortisol [2].
• ANG II can contribute to the regulation of retinal neovascularization by stimulating pericyte migration [3].
• Neuroblastoma x glioma hybrid cells (NG108-15), differentiated by treatment with 1.5% dimethyl sulfoxide (DMSO) and 0.5% fetal bovine serum, were used to measure the effect of angiotensin II and III (ANG II and ANG III) on the generation of inositol polyphosphates [4].
• The stimulation of ecNOS by ANG II may act to protect the lung and maintain low pulmonary artery pressures in the renin-angiotensin model of systemic hypertension [5].

High impact information on BRB

• However, only one of them, Asp-435, was equally important for binding of Ang; the Ki increases produced by mutations of the others were 20- to 93-fold smaller for Ang than for RNase A [6].
• Crystallography and mutagenesis of human Ang have previously shown that its pyrimidine binding site is obstructed by Gln-117, implying that a conformational change is a key part of the mechanism of Ang action [7].
• The capacity of angiogenin (Ang) to induce blood vessel growth is critically dependent on its ribonucleolytic activity [7].
• The Arg-Gly-Asp segment of this site in bovine Ang, which is replaced by Arg-Glu-Asn in human Ang, does not have a conformation typical of an integrin recognition site [7].
• Nuclear translocation of angiogenin in proliferating endothelial cells is essential to its angiogenic activity [8].

Chemical compound and disease context of BRB

• Bovine adrenal zona glomerulosa cells were stimulated with angiotensin II (ANG II) or adenosine 3',5'-cyclic monophosphate under room air control (21% O2-0% CO2), CO2 per se (21% O2-10% CO2), hypoxia per se (10% O2-0% CO2), and the combination of CO2 and hypoxia (10% O2-10% CO2) [9].
• The mitogenic effect of ANG II was not inhibited by pretreatment with pertussis toxin and was mediated by AT1 receptors as indicated by its sensitivity to the subtype-selective antagonist DuP-753 [10].

Biological context of BRB

• Angiogenin is a 14.4-kDa human plasma protein with 65% homology to RNase A that retains the key active site residues and three of the four RNase A disulfide bonds [11].
• A covalent angiogenin/ribonuclease hybrid with a fourth disulfide bond generated by regional mutagenesis [12].
• The structures thus generated were subjected to a rigorous free energy component analysis to arrive at a plausible molecular thermodynamic explanation for the substrate specificity of angiogenin [13].
• These results support a model in which both a surface loop and a catalytic site are necessary for the promotion of blood vessel formation by ANG or RNase [14].
• An overview of the relationship of angiogenin and the other RNases of the superfamily showed that their genes all are in relative close proximity on human chromosome 14 [15].

Anatomical context of BRB

• Inhibition of protein synthesis by angiogenin correlates with degradation of endogenous oocyte tRNA [11].
• The in vivo angiogenic potency of ARH-I is markedly diminished compared with that of angiogenin when examined using the chick chorioallantoic membrane assay [12].
• Angiogenin, a member of the pancreatic-like ribonuclease family with a special biological action (RISBAses), is a basic protein that induces blood vessel formation [16].
• However, angiogenin did not affect the growth of human tumor cell lines, development of cow and mouse embryos and spermatogenicity in mice [16].
• In contrast to RNase A, which was ineffective in all biological activities tested, angiogenin suppressed significantly the proliferation of human lymphocytes stimulated by phytohemagglutinin or concanavalin A or by allogenic human lymphocytes (mixed lymphocyte culture) [16].

Associations of BRB with chemical compounds

• With high molecular weight wheat germ RNA and tRNA, ARH-I is 660- and 300-fold more active than angiogenin, respectively, while with poly(uridylic acid), poly(cytidylic acid), cytidylyl(3'----5')adenosine (CpA), and uridylyl(3'----5')adenosine (UpA) activity is enhanced by about 200-fold [12].
• The effects of Phe versus Ala substitutions show that the key residue Tyr434 interacts with both ligands primarily through its phenyl ring; for Tyr437, the OH group forms the important contacts with RNase A, whereas the phenyl group interacts with Ang [17].
• Retinoic acid and monensin potentiate the cytotoxicity of bovine seminal RNase, Onconase, angiogenin, and human ribonuclease A 100 times or more [18].
• (ii) The structure of T80A-Ang supports the view that Thr80 plays little role in maintaining the obstructive conformation of the C-terminus and that its participation in a hydrogen bond with Thr44 selectively weakens the interaction between Thr44 and N3 of cytosine [19].
• (i) The structure of T44D-Ang indicates that Asp44 can participate directly in pyrimidine binding and that the intrinsic hydrogen-bonding capability of this residue largely governs the pyrimidine specificity of this variant [19].

Physical interactions of BRB

• Binding of angiogenin to its cell-surface binding protein (actin) followed by dissociation of the angiogenin-actin complex from the cell surface and subsequent activation of tissue-type plasminogen activator/plasmin are likely steps involved in the processes of endothelial cell invasion and angiogenesis [20].

Enzymatic interactions of BRB

• Angiogenin catalyzes limited cleavage of 18S and 28S ribosomal RNA and is several orders of magnitude less potent than RNase A toward conventional substrates [12].

Regulatory relationships of BRB

• ANG II stimulates endothelial nitric oxide synthase expression in bovine pulmonary artery endothelium [5].
• We report here that in bovine adrenal fasciculata cells ANG II by itself does not affect growth but inhibits basic fibroblast growth factor (bFGF)-induced DNA synthesis and blocks the cells in G1 phase [21].
• Angiogenin enhances actin acceleration of plasminogen activation [22].

Other interactions of BRB

• We demonstrate that recombinant angiogenin functions as a cytotoxic tRNA-specific RNase in cell-free lysates and when injected into Xenopus oocytes [11].
• Immunosuppressive activity of angiogenin in comparison with bovine seminal ribonuclease and pancreatic ribonuclease [16].
• ANG II-induced chemotaxis is mediated by PDGF-BB and involves TGF-beta, but it is independent of MMP activity [3].
• Although ANG II augmented the latent matrix metalloproteinase-2 (MMP-2) activity of the pericyte by 35%, it also doubled tissue inhibitors of MMPs [3].
• We studied the inhibitory action of atrial natriuretic peptide (4-28 hANP) on the sustained secretory response to ANG II in isolated bovine adrenal glomerulosa cells [23].

Analytical, diagnostic and therapeutic context of BRB

• Site-specific mutagenesis reveals differences in the structural bases for tight binding of RNase inhibitor to angiogenin and RNase A [6].
• The dissection of structure/function elements in ANG reveals a unique opportunity to develop new molecules that modulate neovascularization [14].
• Binding of phosphate and pyrophosphate ions at the active site of human angiogenin as revealed by X-ray crystallography [24].
• Using a new quantitative radio-RNase inhibitor assay, two distinct ribonucleolytic assays, and a radioimmunoassay against angiogenin, it is shown that RNases became apparent in media conditioned by cell monolayers [25].
• The effects of angiotensin II (ANG II) on single K+ channels were studied in rat and bovine adrenal zona glomerulosa (ZG) cells, using the patch-clamp technique [26].

References