The C-terminal Domain Supports a Novel Function for CETPI as a New Plasma Lipopolysaccharide-Binding Protein

Abstract

Described by our group a few years ago, the cholesteryl-ester transfer protein isoform (CETPI), exclusively expressed in the small intestine and present in human plasma, lacked a functional identification for a role of physiological relevance. Now, this study introduces CETPI as a new protein with the potential capability to recognise, bind and neutralise lipopolysaccharides (LPS). Peptides derived from the C-terminal domain of CETPI showed that CETPI not only might interact with several LPS serotypes but also might displace LPS bound to the surface of cells. Peptide VSAK, derived from the last 18 residues of CETPI, protected against the cytotoxic effect of LPS on macrophages. At high concentrations, when different cell types were tested in culture, it did not exhibit cytotoxicity by itself and it did prevent the expression of pro-inflammatory cytokines as well as the generation of oxidative stress conditions. In a rabbit model of septic shock, the infusion of peptide VSAK exerted a protective effect against the effects of LPS and reduced the presence of tumor necrosis factor-alpha (TNFα) in plasma. Therefore, CETPI is proposed as a new protein with the capability to advance the possibilities for better understanding and treatment of the dangerous effects of LPS in vivo.

Modulation of Amyloidogenesis Controlled by the C-Terminal Domain of Islet Amyloid Polypeptide Shows New Functions on Hepatocyte Cholesterol Metabolism

“…However, these changes were not observed when the F 23 R variant was evaluated. Through a standardized assay developed in our group that evaluates lipid–peptide interactions ( 28 , 37 ), samples were processed through native polyacrylamide gradient gels, which evidenced the native interaction among PC vesicles with the C-terminal peptide, a condition that decreased in the F 23 R variant (Figures 5 D,E).…”

“…We established a new methodology through the use of 0.8–15% native gradient gel electrophoresis. Later, gradient gels were stained with Sudan-black and silver protocols, according to previous work ( 28 ).…”

A Novel β-adaptin/c-Myc Complex Formation Modulated by Oxidative Stress in the Control of the Cell Cycle in Macrophages and its Implication in Atherogenesis

“…In a different set of experiments, macrophages received 10 ng/ml LMB stimuli (10 ng/ml) for 4 and 16 h, prior the addition of a gradually increasing concentration of natLDL or oxLDL. These experiments were prolonged for additional 16 h and MTT assays performed according to the protocol previously used 11 , 34 .…”

Lipid Modulation in the Formation of β-Sheet Structures. Implications for De Novo Design of Human Islet Amyloid Polypeptide and the Impact on β-Cell Homeostasis

“…Localized changes in the secondary structure of proteins and peptides are believed to work as a molecular switch regulating function or, in some cases, as a trigger for misfolding. In this context, we have described these conditions by studying the cholesteryl-ester transfer protein (CETP) and a series of apolipoproteins [8][9][10][11][12][13]. In addition, other studies have reported that phosphatidylserine (PS) vesicles could increase the peptide/aggregation ratio, suggesting an electrostatic factor as a triggering condition for the induction of conformational changes [14,15].…”