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Issue title: HNE and Further Lipid Peroxidation Products
Article type: Research Article
Authors: Sunjic, Suzana Borovic | Cipak, Ana | Rabuzin, Filip | Wildburger, Renate | Zarkovic, Neven
Affiliations: Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia | University Clinic of Traumatology, University of Graz, Graz, Austria
Note: [] Address for correspondence: Suzana Borovic Sunjic, Division of Molecular Medicine, Rudjer Boskovic Institute, Bijenicka 54, 10000 Zagreb, Croatia. Tel.: +385 1 4571213; Fax: +385 1 4561010; E-mail: [email protected]
Abstract: The product of lipid peroxidation, 4-hydroxy-2-nonenal (HNE) is known to cause cell death at high concentrations, while at lower concentrations it can influence cell proliferation and differentiation. In our experiments we used human osteosarcoma cells (HOS), to test the influence of HNE on cell proliferation, differentiation and induction of apoptosis. Apoptosis induction was estimated by TiterTACS™ TUNEL test. The cells were in parallel counted and the DAPI staining method was used to distinguish between apoptotic and necrotic cells as well as to define the proportion of cells in mitosis. To test the influence of HNE on HOS cell differentiation, cells were treated every second day with HNE. After 10 days, the cells were stained for alkaline phosphatase, a marker for osteoblast differentiation. Cell growth inhibition was caused by supraphysiological concentrations of 10 or 100 μM HNE, while apoptosis was induced with supraphysiological as well as by the physiological amount of the aldehyde (1 μM). Necrosis appeared when cells were treated with 10 or 100 μM, but not with 1 μM HNE. The proportion of cells in mitosis gradually declined with increased HNE concentration. Multiple exposures of HOS cells to 10 μM HNE prevented HOS cell differentiation. These results indicated that HNE inhibits proliferation and differentiation of HOS cells in the same concentration dependent manner as it causes apoptosis. We thus assume that HNE might be one of the important signaling molecules regulating the growth of the human osteosarcoma cells.
Keywords: 4-Hydroxy-2-nonenal, human osteosarcoma, bone cells, proliferation, differentiation, apoptosis, growth regulation
Journal: BioFactors, vol. 24, no. 1-4, pp. 141-148, 2005
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