Inhibition effects of di(2-ethylhexyl)phthalate on mouse-liver lysosomal vacuolar H+-ATPase

Abstract

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.

TFEB ameliorates DEHP‐induced neurotoxicity by activating GAL3/TRIM16 axis dependent lysophagy and alleviating lysosomal dysfunction

“…DEHP has been demonstrated to induce lysosomal dysfunction in various cell types. For instance, it increases lysosomal membrane permeability in pancreatic β‐cells, 19 and it significantly reduces the level of V‐ATPase in hepatic lysosomes, which is crucial for maintaining the acidic environment within lysosomes 20 . Nonetheless, the relationship between lysosomal dysfunction and DEHP‐induced neurotoxicity needs to be further explored.…”