Identification of an apical sorting determinant in the cytoplasmic tail of megalin

Takeda, Takeshi; Yamazaki, Hajime; Farquhar, Marilyn G.

doi:10.1152/ajpcell.00514.2002

Cited by 115 publications

(82 citation statements)

References 41 publications

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“…2C). In consistence with the previous studies, the decreased serum total protein and albumin indicates loss of these components in the urine as a result of Cdinduced glomerular and tubular injury (Maunsbach 1966, Hjalm et al 1996, Takeda et al 2003, Birn & Christensen 2006. Opposite to the data obtained by Branka et al 2001, Hounkpatin et al 2013, this study has demonstrated a normocytic normochromic anemia observed by marked decreases in RBCs count, Hb concentration, and HCT.…”

Section: Discussionsupporting

confidence: 82%

Protective effect of cinnamon against cadmium-induced hepatorenal oxidative damage in rats

Abdeen

Ghonim

El-Shawarby

et al. 2017

IJPT

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Background: Cadmium (Cd) is a well-known hazardous environmental contaminant. It exerts its toxicity through induction of lipid peroxidation and reduction of cellular antioxidant. Therefore, in this study, we investigated whether cinnamon could protect against Cd toxicity in liver and kidney. Materials and methods: Forty male Wister rats (130-135 gm) were divided randomly into 4 groups/ 10 rats each. Control, cinnamon, cadmium, and Cinn+Cd groups received distilled water, cinnamon extract (200 mg/kg b.wt. orally), cadmium chloride (5 mg/kg b.wt. orally), and Cd plus cinnamon, respectively. Blood, liver, and kidney samples were collected after 8 weeks of treatment. Erythrogram, leukogram, liver and kidney functions, and oxidative status (MDA, CAT, and TAC) were determined. Results and discussion: Cd-treated animals showed significant increases in serum ALT, AST, creatinine, and urea indicating hepatic and renal damage. Cd-induced oxidative stress was observed by marked decease TAC accompanied by increase in MDA which contributed in liver and kidney dysfunction. Co-treatment of Cd with cinnamon has improved the oxidation profile by increasing the TAC and decreasing the lipid peroxidation. Cinnamon ameliorated the toxic effect of Cd, which observed by improvement of liver and kidney functions. Conclusion: High antioxidants content of cinnamon could protect the liver and kidney from Cd toxicity.

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Section: Discussionsupporting

confidence: 82%

Protective effect of cinnamon against cadmium-induced hepatorenal oxidative damage in rats

Abdeen

Ghonim

El-Shawarby

et al. 2017

IJPT

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“…Megalin resembles basolateral proteins in that it recycles quickly between the PM and endosomal compartments, dependent on NPXY-type tyrosine sorting signals that resemble PM endocytic motifs. Interestingly, its apical sorting might also be guided by a cytoplasmic sequence that resembles the NPXY tyrosine motif (Marzolo et al, 2003;Takeda et al, 2003), a puzzling finding that requires further exploration.…”

Section: Carbohydrates As Apical Sorting Determinantsmentioning

confidence: 99%

Apical trafficking in epithelial cells: signals, clusters and motors

Weisz

Rodríguez-Boulan

2009

Journal of Cell Science

279

281

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In the early days of epithelial cell biology, researchers working with kidney and/or intestinal epithelial cell lines and with hepatocytes described the biosynthetic and recycling routes followed by apical and basolateral plasma membrane (PM) proteins. They identified the trans-Golgi network and recycling endosomes as the compartments that carried out apical-basolateral sorting. They described complex apical sorting signals that promoted association with lipid rafts, and simpler basolateral sorting signals resembling clathrin-coated-pit endocytic motifs. They also noticed that different epithelial cell types routed their apical PM proteins very differently, using either a vectorial (direct) route or a transcytotic (indirect) route. Although these original observations have generally held up, recent studies have revealed interesting complexities in the routes taken by apically destined proteins and have extended our understanding of the machinery required to sustain these elaborate sorting pathways. Here, we critically review the current status of apical trafficking mechanisms and discuss a model in which clustering is required to recruit apical trafficking machineries. Uncovering the mechanisms responsible for polarized trafficking and their epithelial-specific variations will help understand how epithelial functional diversity is generated and the pathogenesis of many human diseases.

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“…The objectives of this study, therefore, were to evaluate the human choriocarcinoma (BeWo) cell line as a model to study megalin-mediated placental transport and to assess the uptake kinetics of gentamicin, an AG antibiotic, using this in vitro model. (19). Cells were fed using DMEM (Thermo Scientific, Rockford, IL) supplemented with 10% FBS, 1% nonessential amino acids, and penicillin-streptomycin and incubated at 37°C in an atmosphere of 95% air and 5% CO 2 .…”

Section: Introductionmentioning

confidence: 99%

The Role of Megalin in the Transport of Gentamicin Across BeWo Cells, an In Vitro Model of the Human Placenta

Akour

Kennedy

Gerk

2015

AAPS J

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Abstract. Aminoglycosides (AG) are known to readily cross the placenta, although the mechanisms responsible for placental transport have not been characterized. Megalin is expressed in human placenta, and it is reasonable to speculate, given its role in renal AG uptake, that it is similarly involved in placental transport. However, the role of megalin in placental AG uptake has not been established. An in vitro model to study megalin-mediated placental transport has also not been previously described. The objectives of this study, therefore, were to evaluate the human choriocarcinoma (BeWo) cell line as a model to study megalin-mediated placental transport and to assess the uptake kinetics of gentamicin, an AG antibiotic, using this in vitro model. BeWo cells were grown on Transwell® plates, and megalin expression and functional activity were assessed. Uptake of 3 H-gentamicin was also evaluated in the presence and absence of megalin inhibitors. Expression of megalin protein and mRNA in BeWo cells were confirmed via immunoblot and qPCR analysis. Uptake of fluorescein isothiocyanate (FITC)-labeled bovine serum albumin (BSA) (a megalin substrate) was time-, concentration-, and temperature-dependent consistent with a transporter-mediated process. FITC-BSA uptake was also significantly reduced in the presence of unlabeled gentamicin (a megalin substrate) and sodium maleate (to induce megalin shedding) suggesting that megalin is functionally active in BeWo cells. Gentamicin uptake exhibited time and temperature dependence, saturability and Michaelis-Menten kinetics, all of which suggest a transporter-mediated process. Gentamicin uptake was also significantly reduced in the presence of the megalin inhibitors RAP and EDTA suggesting that megalin is likely involved in gentamicin uptake.

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Identification of an apical sorting determinant in the cytoplasmic tail of megalin

Cited by 115 publications

References 41 publications

Protective effect of cinnamon against cadmium-induced hepatorenal oxidative damage in rats

Protective effect of cinnamon against cadmium-induced hepatorenal oxidative damage in rats

Apical trafficking in epithelial cells: signals, clusters and motors

The Role of Megalin in the Transport of Gentamicin Across BeWo Cells, an In Vitro Model of the Human Placenta

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