Induction of peroxisomal Lon protease in rat liver after di-(2-ethylhexyl)phthalate treatment

Abstract

Previously, we identified a peroxisome-specific isoform of Lon protease using subcellular proteomics. In the present study, we investigated changes in the level of the Lon protease in peroxisomes during recovery from peroxisomal proliferation induced by di-(2-ethylhexyl)phthalate (DEHP) to elucidate the function of peroxisomal Lon protease (PSLP). Following a 2-week treatment with DEHP, the level of PSLP was monitored for 15 days. The amount of protease was greatly increased after the 2-week treatment, followed by a further increase 3 days after cessation of the treatment. Afterward, it decreased and reached the control level on day 15. On the other hand, level peroxisomal beta-oxidation enzymes induced to express by DEHP started to decrease soon after discontinuation of treatment. The results suggest that PSLP functions to degrade beta-oxidation enzymes induced by DEHP during recovery from perxisomal proliferation.

Two Proteases, Trypsin Domain-containing 1 (Tysnd1) and Peroxisomal Lon Protease (PsLon), Cooperatively Regulate Fatty Acid β-Oxidation in Peroxisomal Matrix

“…3), although PsLon is believed to be involved in peroxisomal matrix protein import by virtue of the fact that peroxisomal localization of catalase is compromised by the overexpression of PsLon in HEK293 cells (65). Moreover, PsLon has been suggested to play a role in the degradation of various damaged proteins in peroxisomes based on analysis of a pln mutant of Hansenula polymorpha that is deficient in PsLon (70) and in the rapid clearance of fatty acid ␤-oxidation enzymes in rat hepatic cells after their release from di-(2-ethylhexyl)phthalate-induced peroxisome proliferation (71). Thus, PsLon may be involved in the degradation of several as yet unidentified substrates, including proteins that are involved in peroxisomal matrix protein import as well as those that function in stress responses and under normal conditions.…”

Degradation of excess peroxisomes in mammalian liver cells by autophagy and other mechanisms

“…b Hepatocyte of mutant Atg7 F/F :Mx1 liver. Note the presence of numerous autophagosomes containing peroxisomes in a (arrows), in contrast to their complete absence in the mutant mouse liver cells (b) process from peroxisome-proliferation (Yokota et al 2008). Densitometry and quantitative analysis of immunogold labelling of the enzymes in peroxisome indicate that POLP is markedly induced by the DEHP administration.…”

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“…One of these recently discovered proteins is a peroxisomespeciWc isoform of Lon protease (PSLP), an ATP dependent protease with chaperone-like activity (Kikuchi et al 2004). Yokota et al (2008) now studied changes of the level of this protease in rat liver peroxisomes during recovery from a state of peroxisomal proliferation induced by phthalate esters using Western blotting and quantitative immunoelectron microscopy carried out with a polyclonal antibody generated against PSLP. The authors showed that the amount of PSLP was increased for a longer time period than that of -oxidation enzymes, and suggested that PSLP might have a function in degrading these enzymes during recovery from peroxisomal proliferation.…”