Quercetin, a phytoestrogen and dietary flavonoid, activates different membrane-bound guanylate cyclase isoforms in LLC-PK1 and PC12 cells.
Accumulated evidence suggests that quercetin, a dietary flavonoid, has beneficial effects in protection against cardiovascular diseases and in the inhibition of tumour growth. We have recently shown that antioxidants such as 17beta-estradiol, resveratrol, dithiothreitol and vitamin C activate membrane-bound guanylate cyclase GC-A, a receptor for atrial natriuretic factor (ANF). Since quercetin is a phytoestrogen and potent antioxidant, it is possible that it may activate GC-A or other guanylate cyclase isoforms. We examined whether quercetin activates GC-A or GC-B (the receptor for C-type natriuretic peptide, CNP) in PC12 and porcine kidney proximal tubular LLC-PK1 cells. The results showed that quercetin activated a guanylate cyclase isoform in both cell types. Quercetin inhibited CNP-stimulated GC-B activity, but had little effect on ANF-stimulated GC-A activity in PC12 cells, suggesting that quercetin mainly activates GC-B in PC12 cells. In contrast, CNP had no effect on guanylate cyclase activity in LLC-PK1 cells, indicating that GC-B is not expressed in LLC-PK1 cells. Furthermore, quercetin had a small effect on ANF-stimulated GC-A activity and had no effect on soluble guanylate cyclase activity in LLC-PK1 cells, suggesting that quercetin does not activate GC-A, GC-B or soluble guanylate cyclase in LLC-PK1 cells. However, quercetin did stimulate membrane-bound guanylate cyclase activity in LLC-PK1 cell membranes. These results indicate that quercetin activates the GC-B isoform in PC12 cells, but activates an unknown membrane-bound guanylate cyclase isoform in LLC-PK1 cells.
Department of Medicine, Reproductive Research Center, Shandong Provincial Hospital, Shandong University, Jinan, P. R. China.
Zi-Jiang
ZJ
Chen
Michael
M
Vetter
Geen-Dong
GD
Chang
Shiguo
S
Liu
Chung-Ho
CH
Chang
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D006152:Cyclic GMP / Q000096:biosynthesis; D004789:Enzyme Activation / Q000187:drug effects; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D006162:Guanylate Cyclase / Q000378:metabolism*; D007529:Isoflavones; D007536:Isomerism; D018374:LLC-PK1 Cells; D008566:Membranes / Q000187:drug effects / Q000201:enzymology; D020098:Natriuretic Peptide, C-Type / Q000494:pharmacology; D016716:PC12 Cells; D048789:Phytoestrogens; D028321:Plant Preparations; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D013552:Swine
D004968:Estrogens, Non-Steroidal; D005419:Flavonoids; D007529:Isoflavones; D048789:Phytoestrogens; D028321:Plant Preparations; D020098:Natriuretic Peptide, C-Type; D009320:Atrial Natriuretic Factor; D011794:Quercetin; D006162:Guanylate Cyclase; D006152:Cyclic GMP