No abstract

Mechanisms of Mn-superoxide dismutase (Mn-SOD) expression in human umbilical endothelial cells were investigated by Northern blot analysis, enzyme-linked immunosorbent assay, and immunoelectron microscopy. The Mn-SOD in human endothelial cells was markedly induced by the cytokines tumor necrosis factor (TNF), interleukin-1, and lipopolysaccharide as well as by phorbol esters [12-O-tetradecanoylphorbol 13-acetate (TPA)]. The induction was partially blocked by dexamethasone and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, a potent inhibitor of protein kinase C (PKC). In endothelial cells in which PKC had been desensitized to TPA by pretreatment for 24 h, addition of TNF caused overexpression of Mn-SOD. These facts suggested that at least two separate signal-transducing pathways are involved in expression of the Mn-SOD gene. Immunoelectron-microscopic studies showed that Mn-SOD was localized to the mitochondrial matrix of the capillary vascular endothelial cells of cardiac tissues and cultured endothelial cells. Mn-SOD, which is normally abundant in endothelial cells relative to other cell types, may play an important protective role against stresses such as ischemia and inflammation.

No abstract

The LEC rat is a mutant strain displaying hereditary hepatitis and hepatoma. We established enzyme-linked immunosorbent assays of Cu,Zn- and Mn-superoxide dismutase (Cu,Zn- and Mn-SOD) and measured the levels of both SODs in various organs of LEC and Wistar rats. Mn-SOD concentrations were higher in LEC rats than in Wistar rats in most tissues. Cu,Zn-SOD levels of liver, kidney and intestine were lower in LEC rats than in Wistar rats. Atomic absorbtion techniques indicated that in addition to high Cu concentrations as previously reported, LEC rat livers contained high Fe concentrations relative to those in Wistar rat livers. These data suggest that increased concentrations of Fe and Cu and decreased levels of Cu,Zn-SOD may facilitate the Fenton reaction to produce hydroxyl radicals in the tissues of the LEC rat. To compensate for the decreased scavenging effects due to low levels of Cu,Zn-SOD, an adaptive increase of Mn-SOD may occur in the process of hepatitis and hepatocarcinogenesis in LEC rats.