title: Quercetin stimulates NGF-induced neurite outgrowth in PC12 cells via activation of Na(+)/K(+)/2Cl(-) cotransporter.
abstract: We have recently reported that Na(+)/K(+)/2Cl(-) cotransporter isoform 1 (NKCC1) plays an essential role in nerve growth factor (NGF)-induced neurite outgrowth in PC12D cells. On the other hand, it has been reported that dietary flavonoids, such as quercetin, apigenin, and luteolin, stimulate various ion transporters. In the present report, we investigated the effect of quercetin, a flavonoid, on NGF-induced neurite outgrowth in PC12 cells (the parental strain of PC12D cells). Quercetin stimulated the NGF-induced neurite outgrowth in a dose-dependent manner. Knockdown of NKCC1 by RNAi methods abolished the stimulatory effect of flavonoid. Quercetin stimulated NKCC1 activity (measured as bumetanide-sensitive (86)Rb influx) without any increase in the expression level of NKCC1 protein. The stimulatory effect of quercetin on neurite outgrowth was dependent upon extracellular Cl(-). These observations indicate that quercetin stimulates the NGF-induced neurite outgrowth via an increase in Cl(-) incorporation into the intracellular space by activating NKCC1 in PC12 cell.
authors.affiliation: Department of Molecular Cell Physiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Nakajima
authors.forename: Naomi
authors.initials: N
authors.lastname: Niisato
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Marunaka
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002712:Chlorides / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000378:metabolism*; D016501:Neurites / Q000187:drug effects* / Q000378:metabolism; D016716:PC12 Cells; D011794:Quercetin / Q000494:pharmacology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D028021:Sodium-Potassium-Chloride Symporters / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D064506:Solute Carrier Family 12, Member 2
chemical_list: D000975:Antioxidants; D002712:Chlorides; D009414:Nerve Growth Factors; D034741:RNA, Small Interfering; C578879:Slc12a2 protein, rat; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; D011794:Quercetin