High glucose decreases claudins-5 and -11 in cardiac microvascular endothelial cells: Antagonistic effects of tongxinluo.
Purpose/aim of the study: Claudins-5, -9, and -11 are tight-junction proteins that are mainly expressed in endothelial cells. Their deficiency may lead to cell barrier dysfunction, which is considered as the initiating process and pathological basis of cardiovascular disease in diabetes. We investigated whether high glucose (HG) affects claudins-5, -9, and -11 in human cardiac microvascular endothelial cells (HCMECs), and examined the effects of the traditional Chinese medication tongxinluo (TXL) on these tight junction proteins.


METHODS
HCMECs were exposed to HG with and without TXL treatment, and then mRNA and protein levels of claudins-5, -9, and -11 were examined. The distribution of claudins-5 and -11 was also investigated. Histone H3K9 acetylation (H3K9ac) in claudin-5 and claudin-11 gene promoters, which functions in transactivation, was measured.


RESULTS
We found that HG suppressed claudins-5 and -11 gene expression in HCMECs, and TXL reversed the HG-mediated inhibition of claudins-5 and -11 mRNA and protein expressions. Treatment with high-dose of TXL promoted cell membrane localization of claudins-5 and -11 in HG-stimulated HCMECs. Furthermore, high-dose of TXL blocked the inhibition of H3K9ac in claudin-5 and claudin-11 gene promoters caused by exposure to HG, thus activating gene transcription.


CONCLUSIONS
Our results show that HG suppressed claudins-5 and -11 in HCMECs, and TXL could reverse the HG-induced suppression of claudins-5 and -11 by increasing H3K9ac in their respective gene promoters.
a Department of Biochemistry , Hebei Key Laboratory of Medical Biotechnology , Shijiazhuang , PR China.
Bin
B
Li
b Department of Molecular Biology , Hebei Key Lab of Laboratory Animal, Hebei Medical University , Shijiazhuang , PR China.
Yanning
Y
Li
a Department of Biochemistry , Hebei Key Laboratory of Medical Biotechnology , Shijiazhuang , PR China.
Kun
K
Liu
a Department of Biochemistry , Hebei Key Laboratory of Medical Biotechnology , Shijiazhuang , PR China.
Xiujuan
X
Wang
a Department of Biochemistry , Hebei Key Laboratory of Medical Biotechnology , Shijiazhuang , PR China.
Jinsheng
J
Qi
a Department of Biochemistry , Hebei Key Laboratory of Medical Biotechnology , Shijiazhuang , PR China.
Boya
B
Wang
b Department of Molecular Biology , Hebei Key Lab of Laboratory Animal, Hebei Medical University , Shijiazhuang , PR China.
Yu
Y
Wang
D002478:Cells, Cultured; D062507:Claudin-5 / Q000187:drug effects / Q000378:metabolism*; D057167:Claudins / Q000187:drug effects / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D055806:Microvessels / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*
C120453:CLDN11 protein, human; C107466:CLDN5 protein, human; D062507:Claudin-5; D057167:Claudins; D004365:Drugs, Chinese Herbal; C513941:tongxinluo; D005947:Glucose
Claudin-5; Tongxinluo; claudin-11; high glucose; histone H3K9 acetylation