Synthesis and secretion of retinol-binding protein and transthyretin by cultured retinal pigment epithelium

Ong, David E.; Davis, James; O'Day, William T.; Bok, Dean

doi:10.1021/bi00173a029

Cited by 91 publications

(52 citation statements)

References 52 publications

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“…Rbp4 is expressed in the retinal pigment epithelium. [26][27][28][29] However, little is known about the function of RBP4 in the eye. Quadro et al 30 generated a transgenic mouse strain (hRBP4: mRbp4 − / − ) that expressed human RBP4 under the control of the muscle creatine kinase promoter in the Rbp4 − / − background.…”

Section: Discussionmentioning

confidence: 99%

Severe ocular phenotypes in Rbp4-deficient mice in the C57BL/6 genetic background

Shen

Shi

Suzuki

et al. 2016

Laboratory Investigation

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Retinol-binding protein 4 (RBP4) is a specific carrier for retinol in the blood. In hepatocytes, newly synthesized RBP4 associates with retinol and transthyretin and is secreted into the blood. The ternary transthyretin-RBP4-retinol complex transports retinol in the circulation and delivers it to target tissues. Rbp4-deficient mice in a mixed genetic background (129xC57BL/6J) have decreased sensitivity to light in the b-wave amplitude on electroretinogram. Sensitivity progressively improves and approaches that of wild-type mice at 24 weeks of age. In the present study, we produced Rbp4-deficient mice in the C57BL/6 genetic background. These mice displayed more severe phenotypes. They had decreased a-and b-wave amplitudes on electroretinograms. In accordance with these abnormalities, we found structural changes in these mice, such as loss of the peripheral choroid and photoreceptor layer in the peripheral retinas. In the central retinas, the distance between the inner limiting membrane and the outer plexiform layer was much shorter with fewer ganglion cells and fewer synapses in the inner plexiform layer. Furthermore, ocular developmental defects of retinal depigmentation, optic disc abnormality, and persistent hyaloid artery were also observed. All these abnormalities had not recovered even at 40 weeks of age. Our Rbp4-deficient mice accumulated retinol in the liver but it was undetectable in the serum, indicating an inverse relation between serum and liver retinol levels. Our results suggest that RBP4 is critical for the mobilization of retinol from hepatic storage pools, and that such mobilization is necessary for ocular development and visual function.

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Section: Discussionmentioning

confidence: 99%

Severe ocular phenotypes in Rbp4-deficient mice in the C57BL/6 genetic background

Shen

Shi

Suzuki

et al. 2016

Laboratory Investigation

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“…The protein synthesised in the liver is secreted into the blood, whilst from the choroid plexus epithelium it is secreted into the cerebrospinal fluid, presumably to carry essential TH to the brain (Dickson et al, 1987). TTR expression has been detected in the eye of cattle and sheep Martone, 1988) and in vitro cultures of pigment epithelium of the retina from the rat show synthesis and secretion of TTR into the interphotoreceptor space of the retina (Ong et al, 1994). Low levels of TTR mRNA are also expressed in the rat and human pancreas (Jacobsson et al, 1990).…”

Section: Transthyretin Gene Expressionmentioning

confidence: 99%

Evolution of the Thyroid Hormone-Binding Protein, Transthyretin

Power

Elias

Richardson

et al. 2000

General and Comparative Endocrinology

192

119

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Transthyretin (TTR) belongs to a group of proteins, which includes thyroxine-binding globulin and albumin, that bind to and transport thyroid hormones in the blood. TTR is also indirectly implicated in the carriage of vitamin A through the mediation of retinol-binding protein (RBP). It was first identified in 1942 in human serum and cerebrospinal fluid and was formerly called prealbumin for its ability to migrate faster than serum albumin on electrophoresis of whole plasma. It is a single polypeptide chain of 127 amino acids (14,000 Da) and is present in the plasma as a tetramer of noncovalently bound monomers. The major sites of synthesis of TTR in eutherian mammals, marsupials, and birds are the liver and choroid plexus but in reptiles it is synthesised only in the choroid plexus. The observation that TTR is strongly expressed in the choroid plexus but not in the liver of the stumpy-tailed lizard and the strong conservation of expression in the choroid plexus from reptiles to mammals have been taken as evidence to suggest that extrahepatic synthesis of TTR evolved first. The identification and cloning of TTR from the liver of an amphibian, Rana catesbeiana, and a teleost fish, Sparus aurata, and its absence from the choroid plexus of both species suggest an alternative model for its evolution. Protein modelling studies are presented that demonstrate differences in the electrostatic characteristics of the molecule in human, rat, chicken, and fish, which may explain why, in contrast to TTR from human and rat, TTR from fish and birds preferentially binds triiodo-L-thyronine.

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“…These include kidney, adipose, lacrimal gland, retinal pigment epithelium, testes, and brain (2). It is believed that the synthesis of RBP in extrahepatic tissues serves either to recycle retinol to liver (22)(23)(24)(25) or to facilitate the uptake of retinol by tissues with blood tissue barriers (testes, eyes, and brain) (26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38). However, neither of these possibilities has been tested experimentally.…”

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The role of extrahepatic retinol binding protein in the mobilization of retinoid stores

Quadro

Blaner

Hamberger

et al. 2004

Journal of Lipid Research

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Although the major tissue site of retinol binding protein (RBP) synthesis in the body is the liver, other sites of synthesis have been reported. The physiological role(s) of circulating RBP that is produced and secreted extrahepatically has not been systematically investigated. To address this question, we used as a model a mouse strain (hRBP ؊ / ؊ ) that expresses human RBP (hRBP) cDNA under the control of the mouse muscle creatine kinase promoter in an rbp -null background (RBP ؊ / ؊ ). By comparing hRBP ؊ / ؊ , RBP ؊ / ؊ , and wild-type mice, we asked whether extrahepatic RBP can perform all of the physiological functions of RBP synthesized in the liver. We demonstrate that extrahepatically synthesized hRBP, unlike RBP expressed in liver, cannot mobilize liver retinoid stores. Consistent with this conclusion, we find that circulating hRBP is not taken up by hepatocytes. RBP has been proposed to play an essential role in distributing hepatic retinoids between hepatocytes and hepatic stellate cells. We find, however, that the distribution of retinoid in the livers of the three mouse strains described above is identical. Thus, RBP is not required for intrahepatic transport and storage of retinoid. These and other observations are discussed. -Quadro, L., W. S. Blaner, L. Hamberger, P. M. Novikoff, S. Vogel, R. Piantedosi, M. E. Gottesman, and V. Colantuoni. The role of extrahepatic retinol binding protein in the mobilization of retinoid stores.

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Synthesis and secretion of retinol-binding protein and transthyretin by cultured retinal pigment epithelium

Cited by 91 publications

References 52 publications

Severe ocular phenotypes in Rbp4-deficient mice in the C57BL/6 genetic background

Severe ocular phenotypes in Rbp4-deficient mice in the C57BL/6 genetic background

Evolution of the Thyroid Hormone-Binding Protein, Transthyretin

The role of extrahepatic retinol binding protein in the mobilization of retinoid stores

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