Disease relevance of DNP-SG

• RLIP76 expressed in E. coli was purified by DNP-SG affinity chromatography [1].

High impact information on DNP-SG

• Biliary secretion of the Mrp2 substrate, 2,4-dinitrophenyl-S-glutathione (GS-DNP), was studied in the presence or absence of the PKC inhibitor, bisindolylmaleimide I (BIM-I; 1 micromol/L) [2].
• Both N-RLIP76(1-367) and C-RLIP76(410-655) had ATPase activity (K(m) for ATP, 2.5 and 2.0 mM, respectively) which was stimulated by DNP-SG, DOX, and colchicine (COL) [3].
• In addition, the observation that both mildly cationic or neutral natural product cytotoxic drugs and anionic compounds such as DNP-SG, MK571, and arsenate are competitive inhibitors of MRP action suggests that the substrate specificity of the transporter is quite broad [4].
• Hepatovenous lactate dehydrogenase and alanine aminotransferase efflux as markers of liver integrity and biliary secretion of 2,4-dinitrophenyl-S-glutathione (DNP-GS) were determined photometrically [5].
• Secretion of DNP-SG was not altered in pregnant rats but increased in lactating animals by late lactation [6].

Chemical compound and disease context of DNP-SG

• This study demonstrates that glutathione S-conjugates (2,4-dinitrophenyl-S-glutathione and bimane-S-glutathione) are transported also out of Escherichia coli K12 cells [7].

Anatomical context of DNP-SG

• ATP-dependent efflux routes for 2,4-dinitrophenyl S-glutathione (DNP-SG) were investigated using inside-out vesicles from human erythrocytes [8].
• Rats were injected intravenously with lipopolysaccharides (LPS), and at different times after injection, canalicular transport of 2,4-dinitrophenyl-S-glutathione (GS-DNP), as a model organic anion, was measured in perfused livers and isolated hepatocytes [9].

Associations of DNP-SG with other chemical compounds

• ATP-dependent transport of temocaprilat was competitively inhibited by 2,4-dinitrophenyl-S-glutathione, a typical substrate for cMOAT with an inhibition constant (K(i)) of 25.8 microM [10].
• Membrane vesicles isolated from C-A500 and KCP-4, but not from KB-3-1, exhibited the ATP-dependent uptake of glutathione conjugates (GS-X) such as leukotriene C4 and 2,4-dinitrophenyl-S-glutathione (DNP-SG), indicating the presence of GS-X pumps on these cells [11].
• In erythrocyte inside-out vesicles (IOVs) coated with antibodies against RLIP76, a dose-dependent inhibition of the ATP-dependent transport of DOX and GS-E, including S-(dinitrophenyl)glutathione (DNP-SG), leukotriene C(4), and the GSH conjugate of 4-hydroxynonenal, was observed with a maximal inhibition of about 70% [12].
• The CSF concentration of estradiol-17beta-glucuronide (E(2)17betaG) and 2,4-dinitrophenyl-S-glutathione (DNP-SG) in the CSF after intracerebroventricular and intravenous injection were compared between wild-type and Mrp1 gene knockout mice [13].

Gene context of DNP-SG

• Do multidrug resistance-associated protein-1 and -2 play any role in the elimination of estradiol-17 beta-glucuronide and 2,4-dinitrophenyl-S-glutathione across the blood-cerebrospinal fluid barrier [13]?
• We have previously identified in human tissues a transporter, DNP-SG [S-(2, 4-dinitrophenyl)glutathione] ATPase, capable of carrying out this function [Awasthi et al. (1998) Biochemistry 37, 5231-5238, 5239-5248] [1].
• This ATPase stimulation parallels the uptake of DNP-SG in these vesicles [14].

References