Expression of a Copper Transporter ADP-ribosylation Factor-1 (Arf1) in the Blood-Cerebrospinal Fluid Barrier

Sai DwibhashyamFollow

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Life Sciences

Is this submission part of ICaP/PW (Introductory Composition at Purdue/Professional Writing)?

No

Abstract

ADP-ribosylation factor 1 (Arf1) is a GTP binding protein that functions as a secondary messenger in cell signaling to maintain the Golgi architecture for vesicular trafficking. Copper (Cu) is an essential element indispensable for a variety of cellular enzymatic reactions, and its homeostasis is tightly regulated by Cu-transporting ATPases (Cu-ATPases), i.e., ATP7A and ATP7B. Evidence from this lab and others has established that elevated intracellular Cu levels prompt the translocation of ATP7A from the trans-Golgi network (TGN) towards the plasma membrane to facilitate the efflux of Cu. Moreover, literature data suggest that Arf1 is involved in Cu intracellular trafficking. The choroid plexus in brain ventricles constitute the blood and cerebrospinal fluid (CSF) barrier (BCB), which regulates material transport between the blood and CSF. This study was designed to test the hypothesis that Arf1 is present in brain barrier systems. Using qPCR, we compared the expression of Arf1 in choroidal Z310 cells, brain barrier RBE4 cells, and neuronal dopaminergic N27 cells. Using a western blot, the Arf1 proteins were clearly seen expressed in Z310 cells. Our data clearly showed that mRNAs encoding Arf1 were present in all three cell types. Furthermore, confocal images show Arf1 localization in the Golgi. The function of Arf1 under toxic metal exposures is currently in progress in this lab. The results by far suggest that Arf1 is present in the brain barriers and possibly plays an important role in regulating Cu transport between the blood and CSF/brain parenchyma by modulating ATP7A and/or ATP7B intracellular trafficking. This research is important to our understanding of Cu homeostasis in the central nervous system as affected by environmental exposure and nutritional malfunction.

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Expression of a Copper Transporter ADP-ribosylation Factor-1 (Arf1) in the Blood-Cerebrospinal Fluid Barrier

ADP-ribosylation factor 1 (Arf1) is a GTP binding protein that functions as a secondary messenger in cell signaling to maintain the Golgi architecture for vesicular trafficking. Copper (Cu) is an essential element indispensable for a variety of cellular enzymatic reactions, and its homeostasis is tightly regulated by Cu-transporting ATPases (Cu-ATPases), i.e., ATP7A and ATP7B. Evidence from this lab and others has established that elevated intracellular Cu levels prompt the translocation of ATP7A from the trans-Golgi network (TGN) towards the plasma membrane to facilitate the efflux of Cu. Moreover, literature data suggest that Arf1 is involved in Cu intracellular trafficking. The choroid plexus in brain ventricles constitute the blood and cerebrospinal fluid (CSF) barrier (BCB), which regulates material transport between the blood and CSF. This study was designed to test the hypothesis that Arf1 is present in brain barrier systems. Using qPCR, we compared the expression of Arf1 in choroidal Z310 cells, brain barrier RBE4 cells, and neuronal dopaminergic N27 cells. Using a western blot, the Arf1 proteins were clearly seen expressed in Z310 cells. Our data clearly showed that mRNAs encoding Arf1 were present in all three cell types. Furthermore, confocal images show Arf1 localization in the Golgi. The function of Arf1 under toxic metal exposures is currently in progress in this lab. The results by far suggest that Arf1 is present in the brain barriers and possibly plays an important role in regulating Cu transport between the blood and CSF/brain parenchyma by modulating ATP7A and/or ATP7B intracellular trafficking. This research is important to our understanding of Cu homeostasis in the central nervous system as affected by environmental exposure and nutritional malfunction.