Resveratrol Activates Membrane-bound Guanylate Cyclase in PC12 Cells

Abstract

Resveratrol, found in wine and grapes, has cardioprotective and anticarcinogenic properties. The guanylate cyclase‐cyclic GMP (cGMP) system is known to mediate the effects of vasoactive hormone and ligands such as atrial natriuretic factor and nitric oxide. It is possible that resveratrol exerts its effects by activating guanylate cyclase. This study was conducted to examine whether resveratrol can affect the guanylate cyclase‐cGMP system in PC12 cells. The results showed that resveratrol dose‐dependently increased cGMP levels. It inhibited membrane‐bound guanylate cyclase activity stimulated by atrial natriuretic factor, but had no effect on soluble guanylate cyclase activity stimulated by sodium nitroprusside. It also directly stimulated membrane‐bound guanylate cyclase activity in PC12 cell membranes. These results show that resveratrol increases cGMP formation by activating membrane‐bound, but not soluble, guanylate cyclase.

Quercetin, a phytoestrogen and dietary flavonoid, activates different membrane-bound guanylate cyclase isoforms in LLC-PK1 and PC12 cells

“…Recently, we have shown that 17 -estradiol and resveratrol, a phytoestrogen, activate GC-A in PC12 cells (Chen et al 1998(Chen et al , 2000. Other antioxidants, such as dithiothreitol and vitamin C, also activate GC-A in PC12 cells (Chen et al 2001a).…”

“…The cell extracts were scraped and centrifuged for 15 min at 2000 g, and the supernatant fractions were extracted with water-saturated ether to remove trichloroacetic acid. The cGMP levels in the supernatants were determined by radioimmunoassay (Chang & Song 1993;Chen et al 1998Chen et al , 2000Chen et al , 2001a.…”

“…Reactions were initiated by the addition of LLC-PK1 cell membranes, incubated for 10 min and terminated by the addition of 0.5 mL 50 mM chilled sodium acetate, pH 4.0. Generated cGMP was quantified by the radioimmunoassay as previously described (Chang & Song 1993;Chen et al 1998Chen et al , 2000Chen et al , 2001a.…”

“…Membrane-bound GC-A and GC-B are the receptors for ANF and CNP, respectively (Wedel & Garbers 2001). PC12 cells are known to express GC-A (Chen et al 1998(Chen et al , 2000(Chen et al , 2001a and GC-B (Suga et al 1992), and thus serve as a good cell model system for studying the effects of quercetin on the activity of GC-A and GC-B. To examine whether quercetin activates GC-A or GC-B, we measured the effects of quercetin on ANF-stimulated GC-A and CNP-stimulated GC-B activity in PC12 cells.…”

“…Membrane-bound guanylate cyclase GC-A and GC-B are activated by ANF and CNP, respectively (for review, see Wedel & Garbers 2001). Recently, we have found that antioxidants such as 17 -estradiol, resveratrol (a phytoestrogen), dithiothreitol and vitamin C activate GC-A in PC12 cells (Chen et al 1998(Chen et al , 2000(Chen et al , 2001a. Since quercetin is a potent antioxidant (Soleas et al 1997, Wiseman 1999, Jovanovic & Simic 2000, Lamson & Brignall 2000, and expresses oestrogen-like (Piantelli et al 1995;Caltagirone et al 1997) or anti-oestrogen properties (Miodini et al 1999), we examined whether quercetin affects the activation of GC-A or GC-B.…”