Inhibition effects of di(2-ethylhexyl)phthalate on mouse-liver lysosomal vacuolar H(+)-ATPase.
We investigated the effects of di(2-ethylhexyl)phthalate (DEHP) on mouse-liver lysosomes. After 2 weeks of oral administration in mice, a reduction in vacuolar H(+)-ATPase (V-ATPase) was observed, and after 3 weeks, the liver lysosomal compartment was completely negative for V-ATPase, as determined by immunocytochemical analysis. When the mice were subsequently fed a normal diet for 1 week, V-ATPase levels recovered to normal values. According to Northern blot analysis, V-ATPase subunit A mRNA decreased gradually with DEHP treatment. Enzyme cytochemical staining showed acid phosphatase (AcPase) to be present in lysosomes and late autophagosomes (autolysosomes) in normal animals as well as in DEHP-treated animals. But the number of late autophagosomes containing AcPase increased clearly after DEHP treatment. These results suggest that: (1) DEHP causes marked V-ATPase reduction in the liver lysosomal compartment and the effect of DEHP is reversible; and (2) the effect of DEHP on protein expression is likely to be exerted at the transcriptional level.
Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan.
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D000818:Animals; D015152:Blotting, Northern; D002467:Cell Nucleus / Q000378:metabolism; D004051:Diethylhexyl Phthalate / Q000494:pharmacology*; D015151:Immunoblotting; D007150:Immunohistochemistry; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008247:Lysosomes / Q000201:enzymology* / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008856:Microscopy, Fluorescence; D016253:Microscopy, Immunoelectron; D006180:Proton-Translocating ATPases / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic; D014617:Vacuoles / Q000201:enzymology*
D012333:RNA, Messenger; D004051:Diethylhexyl Phthalate; D006180:Proton-Translocating ATPases