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High glucose-induced membrane translocation of PKC βI is associated with Arf6 in glomerular mesangial cells

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Abstract

Protein kinase C (PKC)-induced changes in glomerular mesangial cell (MC) phenotypic behavior has been implicated in diabetes. The activity of diacylglycerol-sensitive PKC isoforms in MCs is altered by ambient changes in glucose, but the regulation of PKC activity and subsequent intracellular signaling events are not yet clearly defined. Small GTP-binding proteins of the ADP-ribosylation factor (Arfs) family, may regulate protein kinase membrane recruitment and hence its activity in signaling events of non-polarized cells. Members of the ARF family may coordinate membrane dynamics and other cellular functions through their interaction with PKC. We studied the activation of Arf, PKC βI and phospholipase D (PLD) in MCs cultured under normal or high glucose conditions. MCs cultured in high glucose medium exhibited predominantly cytosolic localization of PKC βI, Arf3 and Arf6. However, phorbol ester (PMA) stimulation of cells cultured in high glucose significantly enhanced membrane association of PKC βI and Arf6, but not Arf3. Using [3H]choline chloride to prelabel MCs and measuring [3H]choline-containing metabolite release as PLD activity, PMA-stimulated a significant increase of PLD activity under high glucose condition. Our data suggest that Arf6 plays a specific role in activation of PKC βI and PLD under high glucose condition, and may be a significant intracellular event in the change of the mesangial cell phenotype associated with diabetic nephropathy.

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Authors and Affiliations

  1. Department of Medicine and Department of Pathology, Case Western Reserve University and Louis Stokes Veterans Affairs Medical Center, Cleveland, OH, 44106, USA

    Anoop Kumar Padival & Chunfa Huang

  2. Louis Stokes Veterans Affairs Medical Center, Cleveland, OH, 44106, USA

    Karen S. Hawkins

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  1. Anoop Kumar Padival
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  2. Karen S. Hawkins
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  3. Chunfa Huang
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Padival, A.K., Hawkins, K.S. & Huang, C. High glucose-induced membrane translocation of PKC βI is associated with Arf6 in glomerular mesangial cells. Mol Cell Biochem 258, 129–135 (2004). https://doi.org/10.1023/B:MCBI.0000012847.86529.07

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