Protective effects of transient HO-1 overexpression on susceptibility to oxygen toxicity in lung cells

被引:118
作者
Suttner, DM
Sridhar, K
Lee, CS
Tomura, T
Hansen, TN
Dennery, PA
机构
[1] Stanford Univ, Sch Med, Dept Pediat, Palo Alto, CA 94304 USA
[2] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA
[3] Ohio State Univ, Dept Pediat, Columbus, OH 43210 USA
关键词
heme oxygenase-1; antioxidant; oxidative stress; cell proliferation; nuclear protein;
D O I
10.1152/ajplung.1999.276.3.L443
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Rat fetal lung cells (RFL-6) were transiently transfected with a full-length rat heme oxygenase (HO)-1 cDNA construct and then exposed to hyperoxia (95% O-2-5% CO2) for 48 h. Total HO activity and HO-1 protein were measured as well as cell viability, lactate dehydrogenase (LDH) release, protein oxidation, lipid peroxidation, and total glutathione to measure oxidative injury. HO-1 overexpression resulted in increased total HO activity (2-fold), increased HO-1 protein (1.5-fold), and increased cell proliferation. Immunohistochemistry revealed perinuclear HO-1 localization, followed by migration to the nucleus by day 3. Decreased cell death, protein oxidation, and lipid peroxidation but increased LDH release and glutathione depletion were seen with HO-1 overexpression. Reactive iron content could not explain the apparent loss of cell membrane integrity. With the addition of tin mesoporphyrin, total HO activity was decreased and all changes in injury parameters were normalized to control values. We conclude that moderate overexpression of HO-1 is protective against oxidative injury, but we speculate that there is a beneficial threshold of HO-1 expression.
引用
收藏
页码:L443 / L451
页数:9
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