TY  - JOUR
AU  - Sun, Wen-Tao
AU  - Wang, Xiang-Chong
AU  - Novaković, Aleksandra
AU  - Wang, Jun
AU  - He, Guo-Wei
AU  - Yang, Qin
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3361
AB  - Objectives: We recently reported the involvement of ER stress-mediated BKCa channel inhibition in homocysteine-induced coronary dilator dysfunction. In another study, we demonstrated that tetramethylpyrazine (TMP), an active ingredient of the Chinese herb Chuanxiong, possesses potent anti-ER stress capacity. The present study investigated whether TMP protects BKCa channels from homocysteine-induced inhibition and whether suppression of ER stress is a mechanism contributing to the protection. Furthermore, we explored the signaling transduction involved in TMP-conferred protection on BKCa channels. Methods: BKCa channel-mediated relaxation was studied in porcine small coronary arteries. Expressions of BKCa channel subunits, ER stress molecules, and E3 ubiquitin ligases, as well as BKCa ubiquitination were determined in porcine coronary arterial smooth muscle cells (PCASMCs). Whole-cell BKCa currents were recorded. Results: Exposure of PCASMCs to homocysteine or the chemical ER stressor tunicamycin increased the expression of ER stress molecules, which was significantly inhibited by TMP. Suppression of ER stress by TMP preserved the BKCa beta 1 protein level and restored the BKCa current in PCASMCs, concomitant with an improved BKCa mediated dilatation in coronary arteries. TMP attenuated homocysteine-induced BKCa beta 1 protein ubiquitination, in which inhibition of ER stress-mediated FoxO3a activation and FoxO3a-dependent atrogin-1 and Murf-1 was involved. Conclusions: Reversal of BKCa channel inhibition via suppressing ER stress-mediated loss of beta 1 subunits contributes to the protective effect of TMP against homocysteine on coronary dilator function. Inhibition of FoxO3a-dependent ubiquitin ligases is involved in TMP-conferred normalization of BKCa beta 1 protein level. These results provide new mechanistic insights into the cardiovascular benefits of TMP.
PB  - Elsevier Science Inc, New York
T2  - Vibrational Spectroscopy
T1  - Protection of dilator function of coronary arteries from homocysteine by tetramethylpyrazine: Role of ER stress in modulation of BKCa channels
VL  - 113
SP  - 27
EP  - 37
DO  - 10.1016/j.vph.2018.10.009
ER  - 

@article{
author = "Sun, Wen-Tao and Wang, Xiang-Chong and Novaković, Aleksandra and Wang, Jun and He, Guo-Wei and Yang, Qin",
year = "2019",
abstract = "Objectives: We recently reported the involvement of ER stress-mediated BKCa channel inhibition in homocysteine-induced coronary dilator dysfunction. In another study, we demonstrated that tetramethylpyrazine (TMP), an active ingredient of the Chinese herb Chuanxiong, possesses potent anti-ER stress capacity. The present study investigated whether TMP protects BKCa channels from homocysteine-induced inhibition and whether suppression of ER stress is a mechanism contributing to the protection. Furthermore, we explored the signaling transduction involved in TMP-conferred protection on BKCa channels. Methods: BKCa channel-mediated relaxation was studied in porcine small coronary arteries. Expressions of BKCa channel subunits, ER stress molecules, and E3 ubiquitin ligases, as well as BKCa ubiquitination were determined in porcine coronary arterial smooth muscle cells (PCASMCs). Whole-cell BKCa currents were recorded. Results: Exposure of PCASMCs to homocysteine or the chemical ER stressor tunicamycin increased the expression of ER stress molecules, which was significantly inhibited by TMP. Suppression of ER stress by TMP preserved the BKCa beta 1 protein level and restored the BKCa current in PCASMCs, concomitant with an improved BKCa mediated dilatation in coronary arteries. TMP attenuated homocysteine-induced BKCa beta 1 protein ubiquitination, in which inhibition of ER stress-mediated FoxO3a activation and FoxO3a-dependent atrogin-1 and Murf-1 was involved. Conclusions: Reversal of BKCa channel inhibition via suppressing ER stress-mediated loss of beta 1 subunits contributes to the protective effect of TMP against homocysteine on coronary dilator function. Inhibition of FoxO3a-dependent ubiquitin ligases is involved in TMP-conferred normalization of BKCa beta 1 protein level. These results provide new mechanistic insights into the cardiovascular benefits of TMP.",
publisher = "Elsevier Science Inc, New York",
journal = "Vibrational Spectroscopy",
title = "Protection of dilator function of coronary arteries from homocysteine by tetramethylpyrazine: Role of ER stress in modulation of BKCa channels",
volume = "113",
pages = "27-37",
doi = "10.1016/j.vph.2018.10.009"
}

Sun, W., Wang, X., Novaković, A., Wang, J., He, G.,& Yang, Q.. (2019). Protection of dilator function of coronary arteries from homocysteine by tetramethylpyrazine: Role of ER stress in modulation of BKCa channels. in Vibrational Spectroscopy
Elsevier Science Inc, New York., 113, 27-37.
https://doi.org/10.1016/j.vph.2018.10.009

Sun W, Wang X, Novaković A, Wang J, He G, Yang Q. Protection of dilator function of coronary arteries from homocysteine by tetramethylpyrazine: Role of ER stress in modulation of BKCa channels. in Vibrational Spectroscopy. 2019;113:27-37.
doi:10.1016/j.vph.2018.10.009 .

Sun, Wen-Tao, Wang, Xiang-Chong, Novaković, Aleksandra, Wang, Jun, He, Guo-Wei, Yang, Qin, "Protection of dilator function of coronary arteries from homocysteine by tetramethylpyrazine: Role of ER stress in modulation of BKCa channels" in Vibrational Spectroscopy, 113 (2019):27-37,
https://doi.org/10.1016/j.vph.2018.10.009 . .