Work

Short-term and long-term effects of protein kinase C on the trafficking and stability of human organic anion transporter 3.

Year: 2012

Type: article

Abstract: Human organic anion transporter 3 (hOAT3) belongs to a family of organic anion transporters that play critical roles in the body disposition of numerous clinically important drugs. Therefore, understanding the regulation of this transporter has profound clinical significance. In the current study, we investigated the short-term and long-term regulation of hOAT3 by protein kinase C (PKC). We showed that short-term activation of PKC by phobol 12-Myristate 13-Acetate (PMA) inhibited hOAT3 activity through accelerating its internalization from cell surface to intracellular recycling endosomes. The colocalization of hOAT3 with EEA1-positive recycling endosomes was demonstrated by immunolocalization with confocal microscopy. Furthermore, we showed that long-term activation of PKC resulted in the enhanced degradation of cell surface hOAT3. The pathways for hOAT3 degradation were further examined using proteasomal and lysosomal inhibitors. Our results showed that both proteasomal inhibitors and the lysosomal inhibitors significantly blocked hOAT3 degradation. These results demonstrate that PKC plays critical roles in the trafficking and the stability of hOAT3.

Source: Europe PMC (PubMed Central)

Authors: Qiang Zhang, Wonmo Suh, Zui Pan, Guofeng You

Institution: Rutgers, The State University of New Jersey

Language: English

Topic: Drug Transport and Resistance Mechanisms

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases

Awards: MOLECULAR MECHANISMS OF DRUG/XENOBIOTIC ELIMINATION, Trafficking and Regulation of Drug/Xenobiotic Transporter OAT