MRP3 (encoded by ABCC3
) is a basolateral transporter of BS, glucuronide, and anionic conjugates, including glutathione [11-13].
ATX-LPA axis has been shown to induce chemoresistance by upregulating antioxidant genes, multidrug-resistant transporters (ABCC1, ABCG2, ABCC2, and ABCC3
), aldehyde dehydrogenase 1 (ALDH1), and stem cell maintenance [99, 136].
gene encodes the ATP binding cassette subfamily C member 3 transporter, also known as Multidrug Resistance Protein 3.
As shown in Figure 6, the relative mRNA levels of Abcc3
, Ccnb2, Cyp27b1, Gc, Maob, and Nr1i2 in db/db mice were significantly higher, whereas the mRNA levels of Apoh, Cyp2j13, Esr-1, Cyp7b1, Hsd17b2, Slc7a13, Slco1a1, and Ugt2b37 were lower compared with those in db/m mice (all p < 0.05).
These downstream genes encode (1) antioxidant enzymes such as [gamma]-glutamate cysteine ligase catalytic subunit (GCLC) and regulatory subunit (GCLM), (2) phase II drug-metabolizing enzymes such as heme oxygenase 1 (HMOX1) and NAD(P)H quinone oxidoreductase 1 (NQO1), and (3) multidrug-resistant proteins (MRPs) such as ATP-binding cassette subfamily (ABC) C1 (ABCC1), ABCC2, ABCC3
, and ABCG2 [18-20].
Genotyping analyses of ABCB1 C3435T ABCG2 C421A and ABCC3
C-211T were conducted using the TaqMan methodology.
Quantitative florescent amplification of cDNA of ABCC1 (Hs01561502_m 1), ABCC3
(Hs00978473_ml), and ABCC4 (Hs00988717_m1) was performed using TaqMan Gene Expression Assays (Applied Biosystems, CA).
The authors suggested that some potassium channels may serve as carcinogen exposure indicators and that gene expression of the Abcc3
transporter may serve as a liver tumor marker.
Mice lacking MRP3 (ABCC3
) have normal bile salt transport but altered hepatic transport of endogenous glucoronides.
ABCC1 HsOD219905_ml 16.75 (0.13) ABCC2 Hs00166123_ml 19.57 (0.81) ABCC3
Hs0035B656_ml 16.72 (0.47) ABCC4 Hs00195260_ml 16.80 (0.24) ABCC5 Hs00194701_m1 19.72 (0.16) ABCC6 Hs00184566_m1 19.90 (0.52) ABCC7 Hs00357011_ml n.e.
was downregulated after 6 hr of budesonide and upregulated after 6 hr of the cotreated exposure.