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      Detection of Cell Death of Cultured Mouse Mesangial Cells Induced by Oxidized Low-Density Lipoprotein

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          The objectives of the present study using cultured mouse mesangial cells (MMC) were (1) to evaluate the type of cytotoxicity induced by oxidized (ox) LDL, i.e. apoptosis, necrosis and types of other cell death and (2) to investigate the pathway of cell death under incubation with antioxidants or scavenger receptor (SR) antagonists. LDH release and a morphological examination were used in this study. Trypan blue staining of MMC was performed to detect dead cells in culture. Cytotoxicity of ox-LDL in MMC was found to be dose- and time-dependent. In the morphological study of electron microscopy, three different types of cell death in ox-LDL-treated MMC were identified. In the morphological study with semithin sections, these three types of dead cells were identified at different dosages of ox-LDL. Type 1 or type 2 dead cells were observed in low dose ox-LDL or in middle-dose ox-LDL-treated MMC, respectively. Type 3 dead cells were marked in high dose ox-LDL-treated MMC. It appears that the cells were apoptotic (type 1), necrotic (type 3) and other types (type 2). The cytotoxicity of ox-LDL was not mediated by cellular internalization of ox-LDL via SRs. On the other hand, the cytotoxicity of ox-LDL was inhibited by antioxidants such as α-tocopherol, probucol, N-acetyl-cysteine or glutathione ethyl ester. It is indicated that the pathways of ox-LDL induced cell death were distinct from the pathway via SRs.

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          Oxidative stress as a mediator of apoptosis.

          Many agents which induce apoptosis are either oxidants or stimulators of cellular oxidative metabolism. Conversely, many inhibitors of apoptosis have antioxidant activities or enhance cellular antioxidant defenses. Mammalian cells exist in a state of oxidative siege in which survival requires an appropriate balance of oxidants and antioxidants. Thomas Buttke and Paul Sandstrom suggest that eukaryotic cells may benefit from this perilous existence by invoking oxidative stress as a common mediator of apoptosis.
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            Transcription Factors′ DNA-Binding Activity in Rat Thymocytes Undergoing Apoptosis after Heat-Shock or Dexamethasone Treatment


              Author and article information

              S. Karger AG
              May 1999
              28 April 1999
              : 82
              : 1
              : 51-58
              aDivision of Nephrology, Department of Medicine, Juntendo University School of Medicine, Tokyo, and bFujigotemba Research Laboratories, Chugai Pharmaceutical Co. Ltd., Shizuoka, Japan
              45367 Nephron 1999;82:51–58
              © 1999 S. Karger AG, Basel

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              Page count
              Figures: 7, References: 23, Pages: 8
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              Original Paper

              Cardiovascular Medicine, Nephrology

              Mesangial cells, cultured, Oxidized LDL, Necrosis, Apoptosis


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