A new species of Xenylla Tullberg, 1869 (Collembola: Hypogastruridae) from Central Amazon, Brazil.

A new species of the cosmopolitan genus Xenylla Tullberg, 1869 is herein described and illustrated. The new species, Xenylla hodori sp. nov., from the Amazon Forest of Northern Brazil, resembles X. capixaba Fernandes & Mendonça, 2010 and X. welchi Folsom, 1916 due, the number of eyes, chaetotaxy head and shape of furca. X. hodori sp. nov. is the second species recorded for the Brazilian Amazon Region.

Protein kinase C-δ (PKC-δ) and PKC-α mediate Ca(2+)-dependent increases in CNP mRNA in human vascular cells.

C type natriuretic peptide (CNP) functions as a paracrine/autocrine vasoprotectant. CNP mRNA is up-regulated in human vascular smooth muscle cells (SMC) by PDGF-BB via a protein kinase C (PKC)-dependent pathways, and by general PKC activation with phorbol myristate acetate (PMA). In this report we examine the calcium dependence and isotype specificity of these PKC/CNP pathways. The PKC-δ-specific inhibitor rottlerin blocked the increase in CNP mRNA and immunoreactive CNP following treatment of aortic SMC (AoSMC) with PDGF-BB. A 300-400-fold PMA-induced elevation of CNP transcript levels in AoSMC and a ~40-fold increase in human aortic endothelial cells (HAEC) were reduced by PKC-α- and PKC-δ-, but not PKC-ß-specific inhibitors. siRNA silencing of PKC-δ reduced PDGF-, but not PMA-stimulated CNP transcript in SMC. Inhibition of intracellular Ca(2+) mobilization abolished a PMA-stimulated increase in CNP transcript in both SMC and HAEC. The results of this study show that PDGF increases CNP in SMC via a protein kinase C-δ-dependent pathway. In contrast, PMA increases CNP expression using PKC-α- and PKC-δ-pathways in both SMC and HAEC. A 8-10-fold greater PMA-induced increase in CNP transcript in SMC than in HAEC suggests that smooth muscle cells could be selectively targeted for CNP up-regulation by PKC-α- and PKC-δ-activators.

Regulation of C-type natriuretic peptide expression.

C-type natriuretic peptide (CNP) is a member of the small family of natriuretic peptides that also includes atrial natriuretic peptide (ANP) and brain, or B-type natriuretic peptide (BNP). Unlike them, it performs its major functions in an autocrine or paracrine manner. Those functions, mediated through binding to the membrane guanylyl cyclase natriuretic peptide receptor B (NPR-B), or by signaling through the non-enzyme natriuretic peptide receptor C (NPR-C), include the regulation of endochondral ossification, reproduction, nervous system development, and the maintenance of cardiovascular health. To date, the regulation of CNP gene expression has not received the attention that has been paid to regulation of the ANP and BNP genes. CNP expression in vitro is regulated by TGF-ß and receptor tyrosine kinase growth factors in a cell/tissue-specific and sometimes species-specific manner. Expression of CNP in vivo is altered in diseased organs and tissues, including atherosclerotic vessels, and the myocardium of failing hearts. Analysis of the human CNP gene has led to the identification of a number of regulatory sites in the proximal promoter, including a GC-rich region approximately 50 base pairs downstream of the Tata box, and shown to be a binding site for several putative regulatory proteins, including transforming growth factor clone 22 domain 1 (TSC22D1) and a serine threonine kinase (STK16). The purpose of this review is to summarize the current literature on the regulation of CNP expression, emphasizing in particular the putative regulatory elements in the CNP gene and the potential DNA-binding proteins that associate with them.

Transforming growth factor-beta1 regulation of C-type natriuretic peptide expression in human vascular smooth muscle cells: dependence on TSC22D1.

C-type natriuretic peptide (CNP) possesses nitric oxide-like signaling mechanisms and actions in the vasculature, including the inhibition of fibrosis and vascular remodeling through counterregulation of transforming growth factor-ß (TGF-ß) signaling. The leucine zipper protein transforming growth factor stimulated clone 22 domain 1 (TSC22D1), cloned via its presumed binding to a GC-rich element in the CNP promoter, was the first protein to be described as a CNP transcription factor, but the lack of supporting evidence since its discovery and its lack of a classical DNA-binding site have left in question its role in the regulation of CNP by TGF-ß and other factors. To define a specific role for TSC22D1 in CNP transcription, we have examined the effects of the profibrotic growth factors TGF-ß1 and PDGF-BB on CNP mRNA expression in cultured human vascular smooth muscle cells (SMC) in which TSC22D1 expression was suppressed with small interfering RNA. Results showed that TGF-ß and PDGF-BB significantly increased CNP expression in all three SMC types. Twenty-four-hour TGF-ß-induced elevations in CNP were strongly correlated with changes in TSC22D1 mRNA levels, and both genes exhibited their greatest response to TGF-ß1 in coronary artery SMC. Furthermore, siRNA suppression of TSC22D1 expression in coronary artery and aortic SMC by ∼90% resulted in 45-65% reductions of both PDGF- and TGF-ß-stimulated CNP expression, respectively. These results support a postulated role of TSC22D1 as an enhancer of CNP transcription and suggest that TGF-ß-induced upregulation of CNP expression in SMC may be mediated in part by increased transcription of TSC22D1.

Increased class A scavenger receptor and glomerular lipid precede mesangial matrix expansion in the bGH mouse model.

OBJECTIVE: Elevated neutral lipid content and mRNA expression of class A scavenger receptor (SRA) have been found in the renal cortex of the bovine growth hormone (bGH) mouse model of progressive glomerulosclerosis (GS). We hypothesize that the increased expression of SRA precedes glomerular scarring in this model. DESIGN: Real time RT-PCR and immunofluorescence were employed to measure SRA and collagen types I and IV in the bGH transgenic and control mice at 5 and 12 weeks (wk) of age to determine the chronology of change in SRA expression in relation to glomerular scarring. Alternative mechanisms for increasing glomerular lipid were assessed by measuring mRNA expression levels of low-density lipoprotein receptor (LDL-r), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), and ATP-binding cassette transporter A1 (ABCA1). In addition, the involvement of macrophages in early GS was assessed by CD68 mRNA expression in kidney cortex. RESULTS: Both mRNA and protein levels of SRA were significantly increased in 5-wk bGH compared with control mice, whereas the expression of collagen I and IV was unaltered. Unchanged levels of LDL-r and HMGR mRNA indicate that neither regulated cholesterol uptake via LDL-r nor the cholesterol synthetic pathway played a role in the early lipid increase. The finding of increased ABCA1 expression was an indicator of excess intracellular lipid in the renal cortex of bGH mice at 5 wk. CD68 expression in bGH did not differ significantly from that of controls at 5 wk suggesting that cortical macrophage infiltration was not increased in bGH mice at this time point. CONCLUSION: An early increase in SRA mRNA and protein expression in the bGH kidney precedes glomerular scarring and is independent of macrophage influx.

Lysophosphatidylcholine increases C-type natriuretic peptide expression in human vascular smooth muscle cells via membrane distortion.

C-type natriuretic peptide (CNP) inhibits the migration of vascular smooth muscle cells (VSMC) and related cell types induced by oxidized LDL and its major atherogenic component, lysophosphatidylcholine (LPC). CNP expression is increased in smooth muscle in atherosclerotic and restenotic lesions, but mechanisms underlying this increase have not been elucidated. We therefore investigated the role of LPC in CNP expression in human aortic VSMC. Both LDL and HDL elevated CNP transcript levels approximately 3-fold in VSMC, but not in endothelial cells. Increasing LPC in both VSMC and endothelial cells induced significant elevations in CNP transcript levels that were correlated with the degree of LPC-induced membrane distortion, and that were abolished by stabilizing cell membranes with cholesterol:methyl-beta cyclodextrin complexes or by chelating intracellular Ca2+ with BAPTA/AM. CNP up-regulation in HAoSMC by both LPC and lysophosphatidic acid was dependent on intact tyrosine kinase and protein kinase C (PKC)-signaling, whereas it was independent of these pathways in endothelial cells. LPC-induced up-regulation of CNP mRNA in human VSMC results from membrane damage and Ca2+ influx and subsequent tyrosine kinase and PKC signaling, suggesting a means by which vascular damage by ox-LDL and LPC could initiate CNP-mediated vasoprotection.

Increase of C-type natriuretic peptide expression by serum and platelet-derived growth factor-BB in human aortic smooth muscle cells is dependent on protein kinase C activation.

C-type natriuretic peptide (CNP) is produced by the vascular smooth muscle cells (SMCs) of injured and atherosclerotic arteries, in which it may exert autocrine control over SMCs by binding to its principal receptors, NPR-B and NPR-C, but few studies have examined the factors that regulate CNP expression in human SMCs. In the present report, we show that serum induces significant increases in both CNP and NPR-C transcript levels in human, but not rat SMCs in culture, and that pretreatment with either the general tyrosine kinase inhibitor genistein, the platelet-derived growth factor (PDGF) tyrosine kinase inhibitor AG 1296, or the protein kinase C (PKC) inhibitor GF109203X blocks most of the serum-induced increase in CNP. PDGF-BB also induced significant dose-dependent increases in CNP transcript that correlated temporally with the serum effect on CNP mRNA. Inhibition of several PDGF-BB signaling pathways downstream of receptor activation showed that PKC inhibition with GF109203X was almost as effective as genistein in abolishing the PDGF-BB-induced up-regulation of CNP mRNA. Furthermore, PKC activation by phorbol 12-myristate 13-acetate (PMA) produced an extremely high level of CNP mRNA that was abolished by GF109203X. Immunoreactive CNP was markedly increased in SMCs receiving 10% serum, 20 ng/ml PDGF-BB, or PMA, and was decreased in PDGF-treated and PMA-treated cells by AG 1296 and GF109203X, respectively. This report suggests that in humans, PDGF and other factors signaling through receptor tyrosine kinases and downstream activation of PKC could represent an important control for CNP expression in vascular smooth muscle.