Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human organic anion transporter 4 (hOAT4) belongs to a family of organic anion transporters which play critical roles in the body disposition of clinically important drugs, including anti-HIV therapeutics, anti-tumor drugs, antibiotics, anti-hypertensives, and anti-inflammatories. hOAT4 is expressed in the placenta and kidney. In the current study, we stably transfected hOAT4 into human placental BeWo cells and the functional properties of hOAT4 and its regulation were investigated in these cells. hOAT4-mediated uptake of estrone sulfate, a protypical organic anion for hOAT4, was dose- and time-dependent, and saturable (Km=4.2 microM). The substrate specificity of hOAT4 includes various steroid sulfates, such as beta-estradiol-3,17-disulfate, 17-beta-estradiol-3-sulfate, beta-estradiol-3-sulfate, and dehydroepiandrosterone-3-sulfate (DHEAS), but does not include p-aminohippuric acid (PAH) and tetraethylammonium (TEA). Pre-incubation of hOAT4-expressing BeWo cells with phorbol 12-myristate 13-acetate (PMA) and phorbol 12,13-dibutyrate (PDBu), both of which are protein kinase C (PKC) activators, acutely inhibited the transport activity. The inhibition by PDBu resulted in a decreased Vmax without significant affecting the Km. Establishment of hOAT4-expressing BeWo cells provided useful tool for further pharmacological and molecular biological studies of placental transport of organic anions mediated by this carrier.
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PMID:Functional characterization of a human organic anion transporter hOAT4 in placental BeWo cells. 1625 92

Human organic anion transporter 4 (hOAT4) belongs to a family of organic anion transporters that play critical roles in the body disposition of clinically important drugs, including anti-human immunodeficiency virus therapeutics, anti-tumor drugs, antibiotics, antihypertensives, and anti-inflammatories. hOAT4 is abundantly expressed in the placenta. In the current study, we examined the regulation of hOAT4 by pregnancy-specific hormones progesterone (P(4)) and 17beta-estradiol (E(2)) and by protein kinase C (PKC) in human placental BeWo cells. P(4) induced a time- and concentration-dependent downregulation of hOAT4 transport activity, whereas E(2) had no effect on hOAT4 function. The downregulation of hOAT4 activity by P(4) mainly resulted from a decreased cell surface expression without a change in total cell expression of the transporter, kinetically revealed as a decreased V(max) without significant change in K(m). Activation of PKC by phorbol 12,13-dibutyrate also resulted in an inhibition of hOAT4 activity through a decreased cell surface expression of the transporter. However, P(4)-induced downregulation of hOAT4 activity could not be prevented by treating hOAT4-expressing cells with the PKC inhibitor staurosporine. We concluded that both P(4) and activation of PKC inhibited hOAT4 activity through redistribution of the transporter from cell surface to the intracellular compartments. However, P(4) regulates hOAT4 activity by mechanisms independent of PKC pathway.
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PMID:Regulation of human organic anion transporter 4 by progesterone and protein kinase C in human placental BeWo cells. 1734 44