Prostaglandin E2 (
PGE2), one product of inflammatory reactions, and
PGA1, which is formed during
PGE2 extraction, induce degeneration in
adenosine 3',5'-cyclic monophosphate (cAMP)-induced differentiated
neuroblastoma (NB) cells in culture. The mechanisms of action of
PGE2 on neurodegeneration are not well understood. To investigate this, we have utilized
PGA(1), which mimics the effect of
PGE2 and is very stable in
solution. We have assayed selected markers of oxidative stress such as
heme oxygenase-1 (HO-1),
catalase,
glutathione peroxidase (GPx1), mitochondrial
superoxide dismutase (Mn-SOD-2) and cytosolic
superoxide dismutase (Cu/Zn-SOD-1). The results showed that the treatment of differentiated NB cells with
PGA1 for a period of 48 hr increased the expression of HO-1 and
catalase, decreased the expression of GPx1 and Mn-SOD-2, and did not change the expression of Cu/Zn-SOD-1 as measured by gene array and confirmed by real-time PCR. The
protein levels of HO-1 and GPx1 increased; however, the
protein level of Mn-SOD-2 decreased and the levels of
catalase and Cu/Zn-SOD-1 did not change as determined by Western blot. The increases in the levels of HO-1 and GPx1 reflected an adaptive response to increased oxidative stress, whereas decrease in the level of Mn-SOD-2 may make cells more sensitive to oxidative damage. These data suggest that one of the mechanisms of action of
PGA1 on neurodegeneration may involve increased oxidative stress. This was supported further by the fact that a mixture of
antioxidants (
alpha-tocopherol,
vitamin C,
selenomethionine, and
reduced glutathione), but not the individual
antioxidants, reduced the level of PGA1-induced degeneration in differentiated NB cells. The addition of a single
antioxidant at two or four times the concentration used in the mixture was toxic.