Cholesteryl Ester Transfer Protein Deficiency Causes Slow Egg Embryonation of Schistosoma japonicum

Okumura-Noji, Kuniko; Sasai, Kanna; Zhan, Renli; Kawaguchi, Hitoshi; Maruyama, Haruhiko; Tada, Toyohiro; Takahashi, Hikaru; Okazaki, Mitsuyo; Miida, Takashi; Sakuma, Nagahiko; Kimura, Genjiro; Ohta, Nobuhiro; Yokoyama, Shinji

doi:10.1006/bbrc.2001.5386

Cited by 12 publications

(34 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It must be emphasized that in the apoAITg/CETPTg line no HDL1-sized particles were detected despite high plasma HDL levels, and HDL size changes were mainly confined to the HDL2 fraction upon the coexpression of the CETP transgene (9). Overall, mouse HDL are not so large as those in plasma of human CETPdeficient subjects (33), neither are HDL in plasma from Dahl hyperlipidemic/hypertensive rats (12). In this context, the CETPTg rat line characterized in this study is a unique model that brings new support to a direct link between the presence of a unique apoE-rich HDL1 subpopulation and defective neutral lipid transfers between triglyceride-rich VLDL and cholesteryl ester-rich HDL, as observed in CETP-deficient patients (14).…”

Section: Downloaded Frommentioning

confidence: 91%

“…With regard to human studies, it is worthy to note that in the presence of abundant apoE-rich large HDL1 is a characteristic of hyperalphalipoproteinemia with complete CETP deficiency, with no detectable amounts of these particles in normo-or hyperalphalipoproteinemic subjects with normal or half normal CETP activity (14,16). Unlike rat, wild-type mouse, at least of the C57BL/6 genetic background, does not naturally exhibit elevated amounts of large, apoE-rich HDL1 (8,33) (Fig. 4B).…”

Section: Downloaded Frommentioning

confidence: 99%

See 1 more Smart Citation

Expression of simian CETP in normolipidemic Fisher rats has a profound effect on large sized apoE-containing HDL

Zak

Lagrost

Gautier

et al. 2002

Journal of Lipid Research

View full text Add to dashboard Cite

In order to investigate the direct effect of cholesteryl ester transfer protein (CETP) on the structure and composition of HDL in vivo, simian CETP was expressed in Fisher rat that spontaneously displays high plasma levels of HDL1. In the new CETPTg rat line, the production of active CETP by the liver induced a significant 48% decrease in plasma HDL cholesterol, resulting in a 34% decrease in total cholesterol level ( P Ͻ 0.01 in both cases). Among the various plasma HDL subpopulations, the largest HDL were those mostly affected by CETP, with a 74% decrease in HDL1 versus a significantly weaker 38% decrease in smaller HDL2 ( P Ͻ 0.0001). Apolipoprotein E (apoE)-containing HDL1 were selectively affected by CETP expression, whereas apoA content of HDL remained unmodified. The reduction in the apoE content of serum HDL observed in CETPTg rats compared to controls (53%, P Ͻ 0.02) suggests that apoE in HDL may constitute in vivo a major determinant of their ability to interact with CETP. These results bring new insight into the lack of HDL1 in plasma from CETP-deficient heterozygotes despite their substantial 50% decrease in CETP activity. In addition, they indicate that HDL1 constitute reliable and practicable sensors of very low plasma CETP activity in vivo. Cholesteryl ester transfer protein (CETP) is a plasma glycoprotein that catalyzes an hetero-exchange of cholesteryl esters (CE) and triglycerides (TG) between HDL and apolipoprotein B (apoB) containing lipoproteins (1, 2).Over the last decade, considerable speculations have been emitted on the pro-or anti-atherogenic properties of CETP. Recently, the experimental blockade of CETP in cholesterol-fed rabbits, an animal species with elevated CETP activity and high atherosclerosis susceptibility, by the use of either antisense oligonucleotides (3, 4), chemical inhibitors (5), or vaccination (6) led to a significant decrease in the extent of atherosclerotic lesions. In the mouse, a CETP-deficient species (7), the pro-or antiatherogenic effects of the expression of high levels of human or simian CETP were dependent on the concomitant overexpression of other genes involved in plasma lipoprotein metabolism (8,9,10,11). In the Dahl hyperlipidemic and hypertensive rat, another CETP deficient species, CETP expression produced a significant rise in atherogenic lesions (12). Finally, studies in CETP-deficient patients did not clarify the point as to whether CETP is a pro-or antiatherogenic factor, depending on the population and the metabolic context studied (13).Besides its long-term effect on atherogenesis, CETP also exerts a strong and direct effect on HDL structure and composition. In this context, and from a metabolic point of view, the mouse and rabbit present some limitations, with large HDL1 particles representing only minor comAbbreviations: CETP, cholesteryl ester transfer protein; TC, total cholesterol; TG, triglycerides.

show abstract

Section: Downloaded Frommentioning

confidence: 91%

Section: Downloaded Frommentioning

confidence: 99%

Expression of simian CETP in normolipidemic Fisher rats has a profound effect on large sized apoE-containing HDL

Zak

Lagrost

Gautier

et al. 2002

Journal of Lipid Research

View full text Add to dashboard Cite

show abstract

“…S. japonicum (Yamanashi strain) was maintained by passage through Oncomelania nosophora and BALB/C mice (15,16). The pairs of adult worms were recovered from the portal vein of the infected mice and cultured as 1 pair/well of 12‐well culture plates in RPMI 1640 medium supplemented with 5 or 10% human serum in 5% CO 2 atmosphere, as described previously (10). C57Black/6J mouse serum or lipoprotein‐depleted serum was also used as a supplement in some experiments.…”

Section: Methodsmentioning

confidence: 99%

“…Thus, CETP deficiency may render humans resistant to hepatic maturation of eggs of S. japonicum , a phenomenon central to liver pathology characteristic of schistosomiasis japonica. We proposed that this could be a background behind the high prevalence of CETP deficiency in Far Eastern Asia (10–14).…”

mentioning

confidence: 99%

CD36‐related protein inSchistosoma japonicum: candidate mediator of selective cholesteryl ester uptake from high‐density lipoprotein for egg maturation

Okumura-Noji

Miura

et al. 2012

FASEB j.

Self Cite

View full text Add to dashboard Cite

Familial cholesteryl ester transfer protein (CETP) deficiency is more common in some East Asian populations than elsewhere, suggesting the possibility of a selective advantage of this genetic defect against regional infectious diseases. Historically, infection with the Asian blood fluke Schistosoma japonicum has been endemic in these regions, including Japan. We previously reported that eggs of S. japonicum require cholesteryl ester uptake from normal high-density lipoprotein (HDL) but not from CETP-deficient HDL for their maturation to miracidia, a critical step of the hepatic pathogenesis of schistosomiasis. Herein we show that cholesteryl ester uptake is selective from HDL, and identified CD36-related protein (CD36RP) as a candidate to mediate the reaction. CD36RP was cloned from the adult and the egg developmental stages of S. japonicum, with 1880 bp encoding 506 amino acid residues exhibiting the CD36 domains and two transmembrane regions. Using antibodies against recombinant peptides representing the potential extracellular domains of CD36RP, Western blotting detected a protein with a molecular mass of 82 kDa in the particulate fraction of the adult parasite cells, which was reduced to 62 kDa after N-glycanase treatment. The extracellular domain peptide bound human HDL, as established by immunoblots following nondenaturing gel electrophoresis. Antibodies against the extracellular domain suppressed HDL cholesteryl ester uptake and maturation of the eggs in vitro. CD36RP is a candidate receptor on eggs of S. japonicum that facilitates uptake of HDL cholesteryl ester necessary for egg embryonation and maturation.

show abstract

“…4,23 The human CETP transgenic mice (C57BL/6) were gifts from Japan Tobacco Inc (Tokyo). 24,25 The homozygous LCAT-deficient mice were cross-bred with the highly expressing CETP transgenic mice to produce the F1 mice, and the F2 mice were derived from a total of 15 matings between the F1 mice. The F2 mice were weaned at 3 weeks (nϭ63, 32 males and 31 females).…”

Section: Animalsmentioning

confidence: 99%

Cholesteryl Ester Transfer Protein Expressed in Lecithin Cholesterol Acyltransferase–Deficient Mice

Tsujita²,

Okumura-Noji³

et al. 2002

ATVB

Self Cite

View full text Add to dashboard Cite

Objective-Regulation of plasma cholesteryl ester transfer protein (CETP) concentration was studied in lecithin-cholesterol acyltransferase (LCAT)-knockout mice. Methods and Results-LCAT-knockout mice were cross-bred with CETP transgenic mice. The offspring (nϭ63) were classified for LCAT genotype and plasma CETP levels (no CETP, low CETP, and high CETP). High density lipoprotein (HDL) decreased as LCAT decreased in each CETP-level group. In the lcat(ϩ/ϩ) and lcat(ϩ/Ϫ) mice, plasma CETP varied from 0 to 30 g/mL, whereas it was Ͻ10 g/mL in the lcat(Ϫ/Ϫ) mice. HDL cholesterol and phospholipid decreased and HDL triglyceride and apolipoprotein B increased in CETP in the lcat(ϩ/ϩ) and lcat(ϩ/Ϫ) mice, whereas there was no difference in HDL between low and high CETP. An effect of CETP on HDL was not detected in the lcat(Ϫ/Ϫ) mice because of the absence of mature HDL. Genomic DNA and mRNA of CETP were correlated and were similar in the lcat(Ϫ/Ϫ) and lcat(ϩ/ϩ) mice. Plasma CETP was correlated with its genomic DNA and mRNA, but the slope of the increase was much lower in the lcat(Ϫ/Ϫ) mice. Whereas plasma CETP mostly associates with HDL in the lcat(ϩ/ϩ) mouse, it is found free in the lcat(Ϫ/Ϫ) mouse. Key Words: cholesterol Ⅲ high density lipoprotein Ⅲ lecithin-cholesterol acyltransferase Ⅲ cholesteryl ester transfer protein Ⅲ mice H igh density lipoprotein (HDL) is given a key role in the hypothesis of a cholesterol transport pathway from the peripheral tissues to the liver. Lecithin-cholesterol acyltransferase (LCAT) plays a major role in this process by esterifying free cholesterol (FC) in circulating lipoproteins to maintain a FC gradient between the peripheral cells and the HDL particle surface and, accordingly, to promote FC efflux from the cells. 1 The importance of LCAT in HDL metabolism has been established by identification and characterization of the patients with LCAT deficiency. 2 Mutations in the human LCAT gene cause either familial LCAT deficiency or fish eye disease, which results in the decrease of plasma HDL and accumulation of cholesterol in the cell membrane in certain organs. 2 Disruption of the LCAT gene in mice also exhibits severe reduction of plasma HDL 3,4 and mimics many features of LCAT deficiency in humans. Conclusions-PlasmaThe cholesteryl ester (CE) generated by LCAT and present in the HDL core can be transported directly to the liver by selective uptake 5,6 and/or potentially as a whole particle. 7 Alternatively, HDL CE is transferred to apoB-containing lipoproteins by CE transfer protein (CETP) for liver uptake. 8 CETP is a plasma glycoprotein that mediates transfer/exchange of CE and triglycerides between HDL and apoBcontaining lipoproteins. 9,10 The heteroexchange of CE with triglycerides by CETP leads to the net CE transfer between plasma lipoproteins. 9 This reaction is also one of the key steps of cholesterol transport from the peripheral tissues to the liver. Thus, CETP is involved as much as LCAT in regulation of the plasma HDL level and remodeling of HDL particles. In fact, patients...

show abstract

Cholesteryl Ester Transfer Protein Deficiency Causes Slow Egg Embryonation of Schistosoma japonicum

Cited by 12 publications

References 30 publications

Expression of simian CETP in normolipidemic Fisher rats has a profound effect on large sized apoE-containing HDL

Expression of simian CETP in normolipidemic Fisher rats has a profound effect on large sized apoE-containing HDL

CD36‐related protein inSchistosoma japonicum: candidate mediator of selective cholesteryl ester uptake from high‐density lipoprotein for egg maturation

Cholesteryl Ester Transfer Protein Expressed in Lecithin Cholesterol Acyltransferase–Deficient Mice

Contact Info

Product

Resources

About