101. Nitric oxide (.NO)-induced mitochondrial injury among chicken .NO-generating and target leukocytes.
- Author
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Sung YJ and Dietert RR
- Subjects
- Animals, Arginine analogs & derivatives, Arginine pharmacology, Cell Line, Cell Survival, Chickens, Hypoxanthines pharmacology, Leukocytes cytology, Leukocytes ultrastructure, Lipopolysaccharides pharmacology, Lymphoma metabolism, Lymphoma pathology, Lymphoma ultrastructure, Macrophages cytology, Macrophages metabolism, Macrophages ultrastructure, Mitochondria drug effects, Mitochondria enzymology, NG-Nitroarginine Methyl Ester, Oxidoreductases analysis, Oxidoreductases metabolism, Oxidoreductases physiology, Tumor Cells, Cultured, Leukocytes metabolism, Mitochondria metabolism, Nitric Oxide metabolism, Nitric Oxide pharmacology
- Abstract
In an analysis of nitric oxide (.NO) production and toxicity, chicken macrophage-generated .NO inhibited mitochondrial activity in both .NO-producing macrophages themselves and lymphoid tumor targets. However, differences in targeting of mitochondrial toxicity were observed among these cells. Two chicken macrophage cell lines, HD11 and MQ-NCSU, produced .NO (measured as nitrite) dependent upon concentrations of L-arginine and bacterial endotoxin (lipopolysaccharide). Mitochondrial activity was negatively correlated with the amount of .NO produced. Using a modified MTT assay, .NO induced suppression in two mitochondrial complexes. Mitochondrial activity was significantly suppressed among HD11 cells receiving LPS alone (complex I, 63.0 +/- 5.5% suppression; complex II, 27.9 +/- 5.2%). In contrast, mitochondrial activities in samples receiving LPS plus inhibitor, NG-nitro-L-arginine methyl ester (NAME; 5 mM) or 2,4-diamino-6-hydroxypyrimidine (DAHP; 5 mM), were not significantly different from control values. When HD11 macrophages were cocultured with lymphoblastoid tumor targets, RECC-CU60 (T cell) or LSCC-RP9 (B cell), adding LPS (1 microgram/ml), tumor cell mitochondrial activity was significantly suppressed. In the generator macrophages, complex I was more suppressed than complex II, whereas in lymphoid targets no such difference was observed. These results indicate that .NO inhibits complex I and II mitochondrial activity but that differential targeting can occur among chicken leukocyte populations.
- Published
- 1994
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