2′,5′-Dihydroxychalcone down-regulates endothelial connexin43 gap junctions and affects MAP kinase activation

• Published in: Toxicology (Amsterdam) Vol. 179; no. 1; pp. 51 - 60
• Main Authors: Lee, Yi-Nan, Yeh, Hung-I, Tian, Tin-Yi, Lu, Wen-Wei, Ko, Yu-Shien, Tsai, Cheng-Ho
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 30.09.2002; Amsterdam Elsevier Science
• Subjects: 2′,5′-Dihydroxychalcone; Biological and medical sciences; Blotting, Western; Bones, joints and connective tissue. Antiinflammatory agents; Cell Communication - drug effects; Cells, Cultured; Chalcone - analogs & derivatives; Chalcone - pharmacology; Chalcones; Connexin 43 - biosynthesis; Connexin 43 - genetics; Connexin43; Cyclooxygenase Inhibitors - pharmacology; Down-Regulation - drug effects; Endothelial cells; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Enzyme Activation - drug effects; Enzyme Inhibitors - pharmacology; Flavonoids - pharmacology; Fluorescent Antibody Technique; Gap junction; Gap Junctions - drug effects; Humans; MAP kinase; Medical sciences; Mitogen-Activated Protein Kinases - antagonists & inhibitors; Mitogen-Activated Protein Kinases - metabolism; Pharmacology. Drug treatments; Protease Inhibitors - pharmacology; von Willebrand Factor - metabolism; MAP kinase; Connexin43; 2′,5′-Dihydroxychalcone; Gap junction; Endothelial cells; Human; Endothelial cell; Enzyme; Antiinflammatory agent; Cell junction; Mitogen-activated protein kinase; Cardiovascular disease; In vitro; Biological activity; Antiplatelet agent; Vascular disease; Connexin; Blood vessel; Atherosclerosis; Mechanism of action
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/S0300-483X(02)00289-5

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.