Schrader M, Wodopia R, Fahimi H D
Institute for Anatomy and Cell Biology, Division II (Medical Cell Biology), University of Heidelberg, Heidelberg, Germany.
J Histochem Cytochem. 1999 Sep;47(9):1141-8. doi: 10.1177/002215549904700906.
Peroxisomes in the human hepatoblastoma cell line HepG2 exhibit a high degree of plasticity. Whereas in confluent cultures they appear as small (0.1-0.3 micrometer) spherical particles, they undergo dramatic changes, forming elongated tubules measuring up to 5 micrometer on separation of cells and cultivation at low density. We recently showed that several growth factors, including nerve growth factor (NGF), induce the formation of tubular peroxisomes and that this induction is sensitive to K 252b, a specific tyrosine kinase inhibitor, suggesting the involvement of this signal transduction pathway. Because tyrosine kinase is also involved in signal transduction via the reactive oxygen species (ROS), we have analyzed in this study the effects of UV irradiation, H(2)O(2), and oxygen on tubulation of peroxisomes. UVC irradiation induced a significant increase in formation of tubular peroxisomes (40-50% of cells) and this effect was dose-dependently inhibited by pretreatment with N-acetyl cysteine, confirming the involvement of ROS in the UV effect. Furthermore, H(2)O(2) also directly induced the tubulation of peroxisomes, although to a lesser extent. Finally, cultivation under hypoxic conditions (1.5% O(2)) drastically reduced the inducing effect of fetal calf serum on tubulation of peroxisomes, suggesting the involvement of oxygen-mediated signaling. Taken together, our observations indicate that ROS induce the tubulation of peroxisomes in HepG2 cells. Because peroxisomes harbor most of the enzymes for catabolism of ROS, the tubulation and expansion of the peroxisome compartment could have a cell rescue function against the destructive effects of ROS.
人肝癌细胞系HepG2中的过氧化物酶体表现出高度的可塑性。在汇合培养时，它们呈现为小的（0.1 - 0.3微米）球形颗粒，而在细胞分离并低密度培养时，它们会发生显著变化，形成长达5微米的细长小管。我们最近发现，包括神经生长因子（NGF）在内的几种生长因子可诱导管状过氧化物酶体的形成，并且这种诱导对特异性酪氨酸激酶抑制剂K 252b敏感，这表明该信号转导途径参与其中。由于酪氨酸激酶也通过活性氧（ROS）参与信号转导，我们在本研究中分析了紫外线照射、H₂O₂和氧气对过氧化物酶体小管形成的影响。紫外线C照射导致管状过氧化物酶体形成显著增加（40 - 50%的细胞），并且用N - 乙酰半胱氨酸预处理可剂量依赖性地抑制这种效应，证实了ROS参与紫外线的作用。此外，H₂O₂也直接诱导过氧化物酶体的小管形成，尽管程度较小。最后，在低氧条件（1.5% O₂）下培养显著降低了胎牛血清对过氧化物酶体小管形成的诱导作用，表明氧介导的信号传导参与其中。综上所述，我们的观察结果表明ROS诱导HepG2细胞中过氧化物酶体的小管形成。由于过氧化物酶体含有大多数用于ROS分解代谢的酶，过氧化物酶体区室的小管形成和扩张可能对ROS的破坏作用具有细胞拯救功能。
