Browsing by Author "Sawant, Onkar B."

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    Aster proteins mediate carotenoid transport in mammalian cells
    (National Academy of Science, 2022) Bandara, Sepalika; Ramkumar, Srinivasagan; Imanishi, Sanae; Thomas, Linda D.; Sawant, Onkar B.; Imanishi, Yoshikazu; von Lintig, Johannes; Ophthalmology, School of Medicine
    Some mammalian tissues uniquely concentrate carotenoids, but the underlying biochemical mechanism for this accumulation has not been fully elucidated. For instance, the central retina of the primate eyes displays high levels of the carotenoids, lutein, and zeaxanthin, whereas the pigments are largely absent in rodent retinas. We previously identified the scavenger receptor class B type 1 and the enzyme β-carotene-oxygenase-2 (BCO2) as key components that determine carotenoid concentration in tissues. We now provide evidence that Aster (GRAM-domain-containing) proteins, recently recognized for their role in nonvesicular cholesterol transport, engage in carotenoid metabolism. Our analyses revealed that the StART-like lipid binding domain of Aster proteins can accommodate the bulky pigments and bind them with high affinity. We further showed that carotenoids and cholesterol compete for the same binding site. We established a bacterial test system to demonstrate that the StART-like domains of mouse and human Aster proteins can extract carotenoids from biological membranes. Mice deficient for the carotenoid catabolizing enzyme BCO2 concentrated carotenoids in Aster-B protein-expressing tissues such as the adrenal glands. Remarkably, Aster-B was expressed in the human but not in the mouse retina. Within the retina, Aster-B and BCO2 showed opposite expression patterns in central versus peripheral parts. Together, our study unravels the biochemical basis for intracellular carotenoid transport and implicates Aster-B in the pathway for macula pigment concentration in the human retina.
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    Maternal Choline Supplementation Mitigates Alcohol-Induced Fetal Cranio-Facial Abnormalities Detected Using an Ultrasonographic Examination in A Sheep Model
    (Elsevier, 2019) Sawant, Onkar B.; Birch, Sharla M.; Goodlett, Charles R.; Cudd, Timothy A.; Washburn, Shannon E.; Psychology, School of Science
    Early detection of prenatal alcohol exposure is critical for designing and testing effectiveness of interventional therapeutics. Choline supplementation during and after prenatal alcohol exposure has shown promising benefits in improving outcomes in rodent models and clinical studies. A sheep model of first trimester-equivalent binge alcohol exposure was used in this study to model the dose of maternal choline supplementation used in an ongoing prospective clinical trial involving pregnancies at risk for FASD. Pregnant sheep were randomly assigned to six groups: Saline+Placebo control, Saline+Choline, binge Alcohol+Placebo (light binging), binge Alcohol+Choline, Heavy binge Alcohol+Placebo (heavy binging) and Heavy binge Alcohol+Choline. Ewes received intravenous alcohol or saline on three consecutive days per week from gestational day (GD) 4 to 41 to mimic first trimester-equivalent weekend binge drinking paradigm. Choline (10 mg/kg in the daily food ration) was administered from GD 4 until term. On GD 76, 11 fetal ultrasonographic measurements were collected transabdominally. Heavy binge alcohol exposure reduced fetal Frontothalamic Distance (FTD), Mean Orbital Diameter (MOD) and Mean Lens Diameter (MLD) and increased Interorbital Distance (IOD) and Thalamic Width (TW). Maternal choline supplementation mitigated most of these alcohol-induced effects. Maternal choline supplementation also improved overall fetal femur and humerus bone lengths compared to their respective placebo groups. Taken together these results indicate a potential dose dependent effect that could impact the sensitivity of these ultrasonographic measures in predicting prenatal alcohol exposure. This is the first study in the sheep model to identify biomarkers of prenatal alcohol exposure in-utero with ultrasound and co-administration of maternal choline supplementation.