RNAi inhibits Coriaria lactone-induced MDR1b overexpression in rat brain microvascular endothelial cells.
P-glyprotein (multidrug resistance gene 1, MDR1) was the first isolated and most extensively investigated refractory epilepsy-related drug-resistant protein. Coriaria lactone (CL) can induce P-glyprotein expression of brain capillary and astrocytes in vivo. We established the primary rat brain microvascular endothelial cell (BMECs) models overexpressing P-glycoprotein induced by CL successfully and infected them with adenovirus vector, which carry small interfering RNA (siRNA) designed to target MDR1b. MDR1b mRNA levels and P-glyprotein expression in experimental group decreased significantly 72 h after infection, and the fluorescence intensity of rhodamine within the cells of experimental group increased significantly. So, CL can induce P-glyprotein overexpression in BMECs in vitro, and siRNA can effectively inhibit expression of P-glyprotein and decrease its "pumping out" function. This may offer a new method and rationale for studying the mechanism of refractory epilepsy and relevant gene therapy.
Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, People's Republic China.
Linyu
L
Tian
Lei
L
Chen
Tianhua
T
Yang
Qin
Q
Zhang
Dong
D
Zhou
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000166:cytology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D000097202:ATP-Binding Cassette Sub-Family B Member 4
D018435:ATP Binding Cassette Transporter, Subfamily B; D007783:Lactones; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D000097202:ATP-Binding Cassette Sub-Family B Member 4; C049836:coriaria lactone