TUBULAR PEROXISOMES IN HEPG2 CELLS - SELECTIVE INDUCTION BY GROWTH-FACTORS AND ARACHIDONIC-ACID

We showed recently the plasticity of the peroxisomal compartment in th e human hepatoblastoma cell line HepG2 as evidenced by the presence of elongated tubular peroxisomes measuring up to 5 mu m next to much sma ller spherical or rod-shaped ones (0.1-0.3 mu m). Since the occurrence of tubular peroxisomes in a given cell in culture is synchronized, wi th neighboring cells containing either small spherical or elongated tu bular peroxisomes, cell counting of immunofluorescence preparations st ained for catalase was used for the quantitative assessment of the dyn amics of the peroxisomal compartment and the factors regulating this p rocess. Initial studies revealed that the formation of tubular peroxis omes is primarily influenced by the cell density as well as by lipid-a nd protein-factors in fetal calf serum, being independent of an intact microtubular network. Biochemical studies showed that the occurrence of tubular peroxisomes correlated with the expression of the mRNA for 70 kDa peroxisomal membrane protein (PMP70), but not with that of matr ix proteins. By cultivation of cells in serum- and protein-free media specific factors were identified which influenced the formation of tub ular peroxisomes. Among several growth factors tested, nerve growth fa ctor (NGF) was the most potent one inducing tubular peroxisomes and it s effect was blocked by K252b, a specific inhibitor of neurotrophin re ceptor pathway suggesting the involvement of signal transduction in th is process. Furthermore, from several polyunsaturated fatty acids (PUF A) which all induced tubular peroxisomes, the arachidonic acid (AA) wa s the most potent one. Our observations suggest that tubular peroxisom es are transient structures in the process of rapid expansion of the p eroxisomal compartment which are induced either by specific growth fac tors or by polyunsaturated fatty acids both of which are involved in i ntracellular signaling.