2',5'-Dihydroxychalcone down-regulates endothelial connexin43 gap junctions and affects MAP kinase activation.
We examined the effect of 2',5'-dihydroxychalcone on connexin43 (Cx43) expression and gap-junctional communication in human umbilical vein endothelial cells (HUVEC). The result showed that expression of Cx43 is rapidly reduced by 2',5'-dihydroxychalcone in a dose-dependent manner, Concomitantly, the communication function, determined by fluorescence recovery after photobleaching (FRAP), is decreased. We further investigated whether the mitogen-activated protein (MAP) kinase and the degradation pathway of gap junctions are involved in these processes. Although the change of Cx43 is not affected by the level of fetal calf serum (FCS) used in the medium, activation of MAP kinase varies, depending on the FCS level. At a low level (0.5%), the chalcone inhibits the activation, like PD98059, a specific inhibitor of MAP kinase kinase. However, at a high level (20%), MAP kinase is activated. On the other hand, the chalcone's down-regulating effect on Cx43, while is totally blocked by protease inhibitors leupeptin and N-acetyl-leucyl-norleucinal (ALLN), persists in the presence of PD98059, We concluded that 2',5'-dihydroxychalcone down-regulates Cx43 expression and gap-junctional communication in the HUVEC via enhancement of the proteolysis pathway, and this compound possesses dual effects on MAP kinase activation.
Cardiovascular Division, Department of Internal Medicine, Mackay Memorial Hospital, Mackay Junior College of Nursing, Taipei Medical University, Taipei, Taiwan, ROC.
Yi-Nan
YN
Lee
Hung-I
HI
Yeh
Tin-Yi
TY
Tian
Wen-Wei
WW
Lu
Yu-Shien
YS
Ko
Cheng-Ho
CH
Tsai
D015153:Blotting, Western; D002450:Cell Communication / Q000187:drug effects; D002478:Cells, Cultured; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D047188:Chalcones; D018031:Connexin 43 / Q000096:biosynthesis* / Q000235:genetics; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D017629:Gap Junctions / Q000187:drug effects*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology; D014841:von Willebrand Factor / Q000378:metabolism
C107497:2',5'-dihydroxychalcone; D047188:Chalcones; D018031:Connexin 43; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D005419:Flavonoids; D011480:Protease Inhibitors; D014841:von Willebrand Factor; D002599:Chalcone; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one