کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1925169 1536347 2014 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Protein kinase C restricts transport of carnitine by amino acid transporter ATB0,+ apically localized in the blood–brain barrier
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Protein kinase C restricts transport of carnitine by amino acid transporter ATB0,+ apically localized in the blood–brain barrier
چکیده انگلیسی


• Amino acid transporter B0,+ (ATB0,+) is apically localized in blood–brain barrier.
• ATB0,+ in the blood–brain barrier is controlled by protein kinase C.
• ATB0,+ is inactivated by exclusion from membrane rafts.
• Brain capillary endothelial cells control carnitine gradient.

Carnitine (3-hydroxy-4-trimethylammoniobutyrate) is necessary for transfer of fatty acids through the inner mitochondrial membrane. Carnitine, not synthesized in the brain, is delivered there through the strongly polarized blood–brain barrier (BBB). Expression and presence of two carnitine transporters – organic cation/carnitine transporter (OCTN2) and amino acid transporter B0,+ (ATB0,+) have been demonstrated previously in an in vitro model of the BBB. Due to potential protein kinase C (PKC) phosphorylation sites within ATB0,+ sequence, the present study verified effects of this kinase on transporter function and localization in the BBB. ATB0,+ can be regulated by estrogen receptor α and up-regulated in vitro, therefore its presence in vivo was verified with the transmission electron microscopy. The analyses of brain slices demonstrated ATB0,+ luminal localization in brain capillaries, confirmed by biotinylation experiments in an in vitro model of the BBB. Brain capillary endothelial cells were shown to control carnitine gradient. ATB0,+ was phosphorylated by PKC, what correlated with inhibition of carnitine transport. PKC activation did not change the amount of ATB0,+ present in the apical membrane of brain endothelial cells, but resulted in transporter exclusion from raft microdomains. ATB0,+ inactivation by a lateral movement in plasma membrane after transporter phosphorylation has been postulated.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Archives of Biochemistry and Biophysics - Volume 554, 15 July 2014, Pages 28–35
نویسندگان
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