Afamin is synthesized by cerebrovascular endothelial cells and mediates α‐tocopherol transport across an <i>in vitro</i> model of the blood–brain barrier

Kratzer, Ingrid; Bernhart, Eva; Wintersperger, Andrea; Hammer, Astrid; Waltl, Sabine; Malle, Ernst; Sperk, Günther; Wietzorrek, Georg; Dieplinger, Hans; Sattler, Wolfgang

doi:10.1111/j.1471-4159.2008.05796.x

Cited by 51 publications

(48 citation statements)

References 45 publications

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“…3B). From our real-time PCR, we detected an increase in the expression of Afamin, 23 Caps2, 21,22 Slc2a10, 26,27 Sec14l4, 24,25 and P2rx7 [18][19][20] as well as Neurogenin3 28 in the Pdx1 PB -Isl-1-Myc islets (Fig. 3B).…”

Section: β-Cell Function In Pdx1mentioning

confidence: 95%

“…In this analysis, we were able to detect an increase in Slc2a10 (Glut10), a gene that has been implicated in glucose metabolism and type 2 diabetes, 26,27 increased levels of SEC14L4, a factor that has been implicated to be involved in secretion in organs like salivary gland, prostate and pancreas, 24,25 and a 35-fold increase in Afamin levels, a transporter for α-tocopherol in the CNS. 23 Additionally, P2rx7, a purinergic receptor with implicated function for regulating both endocrine and exocrine pancreas function and Caps2, transgenic mouse line was characterized in our study, which we acknowledged it as a caveat, we are confident that the effects we observe in the Pdx1 PB -Isl-1-Myc mice are due to the elevation of Isl-1 expression as Arx and MafA, two genes that are downregulated in Isl-1 deficient pancreata, 10,11 were increased the islets of the Pdx1 PB -Isl-1-Myc transgenic mice. Animal experiments were approved by the Children's Hospital of Philadelphia's Institutional Animal Care and Use Committee.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, both Caps2 and P2rx7 have implicated functions in regulating secretion by affecting Ca 2+ signaling through binding to Ca 2+ (Caps2) and mediating the effect of ATP (P2rx7), respectively. [18][19][20][21][22] In contrary, while Afamin and Sec14l4 have no known functions in mediating insulin secretion, they have been implicated in transport of α-tocopherol, a form of vitamin E. [23][24][25] Based on their involvement in transport, these proteins may play crucial roles in regulating exocytosis and vesicular transport in islet β-cells. Additionally, with the implicated functions of Slc2a10 (Glut10), a facilitated glucose transporter and Neurogenin3 in maintaining glucose homeostasis, [26][27][28][29][30][31] our study suggest that increased levels of these genes potentially lead to the enhanced β-cell function seen in the Pdx1 PB -Isl-1-Myc transgenic mice.…”

Section: β-Cell Function In Pdx1mentioning

confidence: 99%

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Elevation of transcription factor Islet-1 levels in vivo increases β-cell function but not β-cell mass

Liu

Walp

May

2012

Islets

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Section: β-Cell Function In Pdx1mentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: β-Cell Function In Pdx1mentioning

confidence: 99%

See 1 more Smart Citation

Elevation of transcription factor Islet-1 levels in vivo increases β-cell function but not β-cell mass

Liu

Walp

May

2012

Islets

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“…Kratzer et al discovered afamin expression in cerebrovascular endothelial cells and demonstrated that afamin facilitates vitamin E transport/transfer across the blood-brain barrier in a suitable cell culture model [20], suggesting a role of afamin in the regulation of vitamin E uptake and transport at the blood-brain barrier.…”

Section: Afamin Expression and Occurrence In Human Body Fluidsmentioning

confidence: 98%

Afamin — A pleiotropic glycoprotein involved in various disease states

Dieplinger

2015

Clinica Chimica Acta

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The human glycoprotein afamin was discovered as the fourth member of the albumin gene family. Despite intense research over the last 20 years, our knowledge of afamin's physiological or pathophysiological functions is still very limited. Circulating afamin is primarily of hepatic origin and abundant concentrations are found in plasma, cerebrospinal, ovarian follicular and seminal fluids. In vitro binding studies revealed specific binding properties for vitamin E. A previously performed analytical characterization and clinical evaluation study of an enzyme-linked immunosorbent assay for quantitative measurement of afamin in human plasma demonstrated that the afamin assay meets the quality specifications for laboratory medicine. Comparative proteomics has identified afamin as a potential biomarker for ovarian cancer and these findings were confirmed by quantitative immunoassay of afamin and validated in independent cohorts of patients with ovarian cancer. Afamin has also been investigated in other types of carcinoma. Most of these studies await further evaluation with validated quantitative afamin assays and require validation in larger patient cohorts. Transgenic mice overexpressing the human afamin gene revealed increased body weight and increased blood concentrations of lipids and glucose. These transgenic mouse data were in line with three large human population-based studies showing that afamin is strongly associated with the prevalence and development of the metabolic syndrome. This review summarizes and discusses the molecular, biochemical and analytical characterization of afamin as well as possible clinical applications of afamin measurement.

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“…The role of afamin remains to be determined; however, afamin is considered to influence the uptake and transport of a-tocopherol at the blood-brain barrier, and is thought to have neuroprotective activity (41,42). In the current study, hepatic afamin expression decreased in STZ rats, and therefore the levels of a-tocopherol in distributed fluids are considered to be low in type 1 diabetes.…”

Section: Discussionmentioning

confidence: 70%

α-Tocopherol Status and Altered Expression of α-Tocopherol-Related Proteins in Streptozotocin-Induced Type 1 Diabetes in Rat Models

Takitani

Inoue

Koh

et al. 2014

Journal of Nutritional Science and Vitaminology, J Nutr Sci Vit

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Vitamin E is a fat-soluble antioxidant that comprises 4 tocopherols (a-, b-, g-, and d-) and 4 tocotrienols (a-, b-, g-, and d-). Of all these vitamin E subtypes, a-tocopherol is the most well-known for its antioxidant activity (1). Lipid-soluble vitamin E has a critical role as an antioxidant protecting the lipids of the plasma membranes and lipoproteins from peroxidation. Dietary vitamin E, including tocopherols and tocotrienols, which are components of bile salt micelles, is absorbed in the intestine. Vitamin E, along with lipids, is incorporated into nascent chylomicrons within the enterocyte, and these chylomicrons are then secreted into the lymphatics and blood vessels (2). After transporting dietary lipids to other locations in the body, chylomicrons are returned to and taken up by the liver. In the liver, a-tocopherol selectively binds to a-tocopherol transfer protein (a-TTP) and is incorporated into very low-density lipoproteins (VLDL). a-TTP is a hepatic cytosolic protein, which facilitates the transport of a-tocopherol to the plasma membrane for the secretion of a-tocopherol into VLDL (1). a-TTP has a critical role in maintaining circulatory a-tocopherol levels. a-TTP gene disrupted mice reveal markedly reduced plasma a-tocopherol levels; moreover, the mutation of the human a-TTP gene is responsible for ataxia with vitamin E deficiency (1, 2). The ATPbinding cassette transporter-1 (ABCA-1), which transports cholesterol and phospholipids, facilitates the secretion of a-tocopherol in the plasma membrane. VLDL, including a-tocopherol, in circulation is lipolysed into low-density lipoprotein (LDL) by lipoprotein lipase, and this LDL is taken up into the peripheral tissues via the action of the LDL receptor. The mechanism of a-tocopherol metabolism has been recently determined (2). The catabolism of tocopherols and tocotrienols is mediated by cytochrome P450 4F2 (CYP4F2), and the resulting metabolite, carboxyethyl hydroxychroman (CEHC), is excreted in urine as glucuronic conjugates.Diabetes is a metabolic disorder pertaining to glucose uptake due to a lack of insulin production by pancreatic b-cells (type 1 diabetes), or it manifests as peripheral insulin resistance, including adipose tissue and muscles (type 2 diabetes). The production of reactive oxygen species (ROS) is the major pathogenesis of diabetes and its complications. Hyperglycemia leads to an increased release of ROS in peripheral tissues (3). In experimental studies, vitamin E supplementation improved the Summary Vitamin E plays a critical role as an antioxidant in several pathological conditions, including diabetes, cancer, cardiovascular diseases, and neurodegenerative disorders. Diabetes is a metabolic disorder of glucose due to the lack of adequate insulin production (type 1) or peripheral insulin resistance (type 2). Oxidative stress plays a major role in the pathogenesis of diabetes and its complications. The purpose of the present study was to determine a-tocopherol status and the expression of a-tocopherol-related proteins, including ...

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Afamin is synthesized by cerebrovascular endothelial cells and mediates α‐tocopherol transport across an in vitro model of the blood–brain barrier

Cited by 51 publications

References 45 publications

Elevation of transcription factor Islet-1 levels in vivo increases β-cell function but not β-cell mass

Elevation of transcription factor Islet-1 levels in vivo increases β-cell function but not β-cell mass

Afamin — A pleiotropic glycoprotein involved in various disease states

α-Tocopherol Status and Altered Expression of α-Tocopherol-Related Proteins in Streptozotocin-Induced Type 1 Diabetes in Rat Models

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Afamin is synthesized by cerebrovascular endothelial cells and mediates α‐tocopherol transport across an in vitro model of the blood–brain barrier

Cited by 51 publications

References 45 publications

Elevation of transcription factor Islet-1 levels in vivo increases β-cell function but not β-cell mass

Elevation of transcription factor Islet-1 levels in vivo increases β-cell function but not β-cell mass

Afamin — A pleiotropic glycoprotein involved in various disease states

&alpha;-Tocopherol Status and Altered Expression of &alpha;-Tocopherol-Related Proteins in Streptozotocin-Induced Type 1 Diabetes in Rat Models

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α-Tocopherol Status and Altered Expression of α-Tocopherol-Related Proteins in Streptozotocin-Induced Type 1 Diabetes in Rat Models