ABC transporter expression profiling after ischemic reperfusion injury in mouse kidney

Abstract

Renal ATP binding cassette (ABC) transporters have an important role in the elimination of metabolic waste products and compounds foreign to the body. The kidney has the ability to tightly control the expression of these efflux transporters to maintain homeostasis, and as a major mechanism of adaptation to environmental stress. In the present study, we investigated the expression of 45 ABC transporter genes in the mouse kidney under basal conditions, after induction of ischemia and after regeneration. Two days after clamping, mice showed a 76% decrease in renal creatinine clearance, which improved clearly within 7 days. This was confirmed by histological examinations. Seven days after ischemia, real-time quantitative Polymerase chain reaction data showed that transcript abundance of abcb1, abcb11, and abcc4 was increased, and that of abca3, abcc2, and abcg2 decreased. Expression of all transporters returned to baseline after 14 days, except for abcb11, which was reduced. Abcb11 is the major liver canalicular bile salt export pump. Here we show for the first time expression in the kidney and localization of the transporter to the apical membrane of proximal tubules. The presence of another novel renal transporter, abca3, was confirmed by Western blotting. Immunohistochemistry showed that abca3 is localized to the peritubular capillaries and apical membrane of proximal tubules. In conclusion, after inducing ischemic reperfusion injury in the kidney, ABC transporters appear to be differentially regulated, which might be associated with the renal regeneration process. Furthermore, we showed for the first time expression and subcellular localization of abcb11 and abca3 in mouse kidney.

Purinergic signaling in the lumen of a normal nephron and in remodeled PKD encapsulated cysts

“…It is well known that the proximal tubule is enriched in the expression of ATP-binding cassette (ABC) transporters [22][23][24][25]. In particular, the multiple organic anion transporters (MOATs) are expressed in abundance [22][23][24][25]. Their principal function is the secretion of large organic anions [22][23][24][25], of which ATP is a principal one.…”

“…Upon chronic administration of a significant dose of one or more drugs in a human patient with a disease condition, the multidrug resistance (mdr) transporters [known as Pglycoprotein (PGP), etc.] will be upregulated and may also be a robust transporter conduit for ATP and other large anions [22][23][24][25]. This minireview does not revisit the debate concerning the role of ABC transporters in ATP transport and release; however, past reviews of this biology are cited here for interested parties [13-15, 26, 27].…”

“…In particular, the multiple organic anion transporters (MOATs) are expressed in abundance [22][23][24][25]. Their principal function is the secretion of large organic anions [22][23][24][25], of which ATP is a principal one. Upon chronic administration of a significant dose of one or more drugs in a human patient with a disease condition, the multidrug resistance (mdr) transporters [known as Pglycoprotein (PGP), etc.]…”

“…The classic example is para-amino hippurate (PAH), which is often used as a marker for PCT secretion [4][5][6]. It is well known that the proximal tubule is enriched in the expression of ATP-binding cassette (ABC) transporters [22][23][24][25]. In particular, the multiple organic anion transporters (MOATs) are expressed in abundance [22][23][24][25].…”

“…Proximal-tubule-based large anion secretion Drug secretion and organic acid secretion also occur in the proximal tubule [22][23][24][25]. The classic example is para-amino hippurate (PAH), which is often used as a marker for PCT secretion [4][5][6].…”