Interactions amongst plasma retinol-binding protein, transthyretin and their ligands: implications in vitamin A homeostasis and transthyretin amyloidosis

Pullakhandam, Raghu; Sivakumar, B.

doi:10.1016/j.bbapap.2004.09.023

Cited by 80 publications

(71 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This structure-function relationship was further strengthened by the observation that TTR knockout mice exhibit lower plasma RBP4 levels and higher urinary excretion of RBP4 (3,4). Furthermore, in vitro studies demonstrated that retinol-RBP4 complex, but not apo-RBP, binds to TTR (3). In tune with these results, fenretinide, a drug that competes with retinol for binding to RBP4, inhibits its interaction with TTR and increases its renal clearance (3,5).…”

Section: Role Of Rbp4 and Ttr In Vitamin A Metabolismmentioning

confidence: 93%

“…In tune with these results, fenretinide, a drug that competes with retinol for binding to RBP4, inhibits its interaction with TTR and increases its renal clearance (3,5). Interestingly, knockouts of either RBP4 or TTR are viable, suggesting the existence of efficient compensatory mechanisms for the transport of retinol and thyroid hormones (3,4).…”

Section: Role Of Rbp4 and Ttr In Vitamin A Metabolismmentioning

confidence: 94%

“…It is believed that such protein-protein interaction increases the apparent molecular mass of RBP4-TTR complex and thus prevents its loss through glomerular filtration. This structure-function relationship was further strengthened by the observation that TTR knockout mice exhibit lower plasma RBP4 levels and higher urinary excretion of RBP4 (3,4). Furthermore, in vitro studies demonstrated that retinol-RBP4 complex, but not apo-RBP, binds to TTR (3).…”

Section: Role Of Rbp4 and Ttr In Vitamin A Metabolismmentioning

confidence: 95%

“…Retinol is an essential component in the physiology of vision and plethora of other biological functions (3,4). As retinol is insoluble in water, it is transported by RBP4, a 20-kDa protein, from its storage site liver to the various target tissues.…”

Section: Role Of Rbp4 and Ttr In Vitamin A Metabolismmentioning

confidence: 99%

“…In the blood, RBP4 circulates as a complex with thyroxine-binding protein, the transthyretin (TTR), which increases the apparent molecular mass of RBP4 complex, and thus prevents its glomerular filtration (3,4). Recently, RBP4 expression in adipocytes has been reported to be related to its plasma levels.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Contrasting effects of type 2 and type 1 diabetes on plasma RBP4 levels: The significance of transthyretin

et al. 2012

View full text Add to dashboard Cite

SummaryRetinol-binding protein 4 (RBP4) is the principle carrier of retinol in the human plasma, which circulates as a complex with transthyretin (TTR), a homotetrameric thyroxine transport protein. Although this complex formation is thought to prevent glomerular filtration of RBP4, it also stabilizes the quaternary structure of TTR. Recent studies indicate elevated plasma levels of RBP4 in type 2 diabetes (T2D). In contrast, reduced RBP4 levels were observed in type 1 diabetes (T1D). Herein, we critically examine the probable mechanisms involved in the regulation of RBP4 and TTR levels during T2D and T1D. The available evidences point to the involvement of pancreatic factors in regulating the expression of both RBP4 and TTR. It appears that during T1D, TTR levels are reduced and it exists predominantly as a monomer that may interfere its interaction with RBP4 resulting in its loss through glomerular filtration. However, plasma TTR levels remain high under T2D conditions and thus reducing glomerular filtration of RBP4. Therefore, the plasma TTR levels appear to be an important determinant of plasma RBP4 levels in these two diabetic conditions. 2012 IUBMB IUBMB Life, 64(12): 975-982, 2012

show abstract

Section: Role Of Rbp4 and Ttr In Vitamin A Metabolismmentioning

confidence: 93%

Section: Role Of Rbp4 and Ttr In Vitamin A Metabolismmentioning

confidence: 94%

Section: Role Of Rbp4 and Ttr In Vitamin A Metabolismmentioning

confidence: 95%

Section: Role Of Rbp4 and Ttr In Vitamin A Metabolismmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Contrasting effects of type 2 and type 1 diabetes on plasma RBP4 levels: The significance of transthyretin

et al. 2012

View full text Add to dashboard Cite

show abstract

Identification of Transthyretin Cardiac Amyloidosis Using Serum Retinol-Binding Protein 4 and a Clinical Prediction Model

et al. 2017

View full text Add to dashboard Cite

Importance Transthyretin amyloid cardiomyopathy (ATTR) is an under-recognized cause of heart failure (HF) in the elderly, owing in part to difficulty in diagnosis. ATTR can result from mutant TTR protein with one of the most common mutations in the United States, V122I, present in 3.43% of African Americans. Objective To determine whether serum retinol-binding protein 4 (RBP4), an endogenous TTR ligand, could be used as a diagnostic test for ATTR V122I amyloidosis. Design Combined prospective and retrospective cohort study Setting Tertiary care referral center Participants Fifty prospectively genotyped African American patients over age 60 years with non-amyloid HF and cardiac wall thickening, and a comparator cohort of biopsy proven ATTR V122I amyloidosis patients (n=25) comprised the development cohort. Twenty-seven prospectively genotyped African American patients and 9 ATTR V122I amyloidosis patients comprised the validation cohort. Main Outcomes and Measures Circulating RBP4, TTR, B-type natriuretic peptide (BNP) and troponin I (TnI) concentrations, electrocardiography (ECG), echocardiography, and clinical characteristics were assessed in all patients. Receiver operating characteristic (ROC) analysis was performed to identify optimal thresholds for ATTR V122I amyloidosis identification. A clinical prediction rule was developed using penalized logistic regression, evaluated using ROC analysis and validated in an independent cohort of cases and controls. Results Age, gender, BNP and TnI were similar between ATTR V122I amyloidosis patients and controls. Serum RBP4 concentration was lower in patients with ATTR V122I amyloidosis compared to non-amyloid controls (31.5 vs. 49.4 ug/ml, p < 0.001) and the difference persisted after controlling for potential confounding parameters. Left ventricular ejection fraction (LVEF) was lower in ATTR V122I amyloidosis (40% vs. 57%, p<0.001), while interventricular septal diameter (IVSd) was higher (16 vs. 14 mm, p<0.001). ROC analysis identified RBP4 as a sensitive identifier of ATTR V122I amyloidosis (AUC 0.78). A clinical prediction algorithm comprised of RBP4, TTR, LVEF, IVSd, mean limb lead ECG voltage and grade 3 diastolic dysfunction yielded excellent discriminatory capacity for ATTR V122I amyloidosis (AUC 0.97), while a 4 parameter model including RBP4 concentration retained excellent discrimination (AUC 0.92). The models maintained excellent discrimination in the validation cohort. Conclusions and Relevance A prediction model employing circulating RBP4 concentration and readily available clinical parameters accurately discriminated ATTR V122I amyloid cardiomyopathy from non-amyloid HF in a case matched cohort. We propose that this clinical algorithm may be useful for identification of ATTR V122I amyloidosis in elderly, African American patients with heart failure.

show abstract

Synthetic Function

Weisiger¹,

DeSancho²,

Pastores³

et al. 2007

Textbook of Hepatology

View full text Add to dashboard Cite

Interactions amongst plasma retinol-binding protein, transthyretin and their ligands: implications in vitamin A homeostasis and transthyretin amyloidosis

Cited by 80 publications

References 75 publications

Contrasting effects of type 2 and type 1 diabetes on plasma RBP4 levels: The significance of transthyretin

Contrasting effects of type 2 and type 1 diabetes on plasma RBP4 levels: The significance of transthyretin

Identification of Transthyretin Cardiac Amyloidosis Using Serum Retinol-Binding Protein 4 and a Clinical Prediction Model

Synthetic Function

Contact Info

Product

Resources

About