Zj. Chen et al., Antioxidants vitamin C and dithiothreitol, activate membrane-bound guanylate cyclase in PC12 cells, J PHARM PHA, 53(2), 2001, pp. 243-247
Antioxidants and antioxidant enzymes are known to protect against cell deat
h induced by reactive oxygen species. However, apart from directly quenchin
g free radicals, little is known about the effect of antioxidants on hormon
e-activated second messenger systems. We previously found that antioxidants
such as 17-beta estradiol and resveratrol activate membrane-bound guanylat
e cyclase CC-A, the receptor for atrial natriuretic factor (ANF), in PC12 c
ells. It is possible that other antioxidants may also activate membrane-bou
nd guanylate cyclase CC-A. The aim of this study was to determine if dithio
threitol (DTT), vitamin C, and vitamin E activate membrane-bound guanylate
cyclase GC-A in PC12 cells. The results showed that both DTT and vitamin C
increased cGMP levels in PC12 cells, whereas vitamin E had no effect. DTT a
nd Vitamin C inhibited membrane-bound guanylate cyclase activity stimulated
by ANF in PC12 cells. In contrast, DTT and Vitamin C had no effect on solu
ble guanylate cyclase activity stimulated by substance P. Furthermore, NO s
ynthase inhibitors L-NAME and aminoguanidine did not affect DTT- and vitami
n C-stimulated guanylate cyclase activity. The results indicate that DTT an
d vitamin C, but not vitamin E, activate membrane-bound guanylate cyclase G
C-A in PC12 cells.