Lysosomal sulfate transport: inhibitor studies.
Sulfate derived from the degradation of macromolecules is released from lysosomes via a carrier mediated process. In order to further characterize this process, recognized inhibitors of the erythrocyte band 3 anion transporter were examined for their effects on the lysosomal system. Studies with band 3 transport site inhibitors such as DIDS, SITS and phenylglyoxal indicated that, similar to the case for the band 3 protein, the lysosomal transporter has critical lysine and arginine residues. Band 3 translocation pathway or channel blocking inhibitors had mixed effects on the lysosomal system. 1,2-Cyclohexanedione, which covalently modifies a band 3 arginine residue distinct from that modified by phenylglyoxal, inhibited lysosomal sulfate transport. In contrast, the potent band 3 inhibitor dipyridamole had no effect on lysosomal sulfate transport indicating that there are some structural differences between the erythrocyte and lysosomal anion transporters. The band 3 translocation inhibitors niflumic acid and dinitrofluorobenzene were both effective inhibitors of the lysosomal system. Cupric ion inhibited sulfate transport while Ca2+, Co2+, Mg2+, Mn2+, and Zn2+ had no inhibitory effects. Exposure of intact lysosomes to trypsin largely ablated transport of sulfate. This information should be useful in efforts to further elucidate the structure and function of the lysosomal sulfate transporter.
Koetters
P J
PJ
Department of Pediatrics, Harbor-UCLA Medical Center, Torrance 90502, USA.
Chou
H F
HF
Jonas
A J
AJ
D000818:Animals; D001457:Anion Exchange Protein 1, Erythrocyte / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D002412:Cations; D005260:Female; D007425:Intracellular Membranes / Q000378:metabolism; D017136:Ion Transport / Q000187:drug effects; D008247:Lysosomes / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013431:Sulfates / Q000378:metabolism*; D014357:Trypsin
D001457:Anion Exchange Protein 1, Erythrocyte; D002412:Cations; D013431:Sulfates; D014357:Trypsin