Effect of tetramethylpyrazine (TMP) on Ca2+ signal transduction and cell viability in a model of renal tubular cells |
| |
| Authors: | Yi‐Chien Fang Chiang‐Ting Chou Wei‐Zhe Liang Chun‐Chi Kuo Shu‐Shong Hsu Jue‐Long Wang Chung‐Ren Jan |
| |
| Affiliation: | 1. Department of Laboratory Medicine, Zuoying Branch of Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan;2. Department of Nursing, Division of Basic Medical Sciences, Chang Gung University of Science and Technology, Chia‐Yi, Taiwan;3. Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Chia‐Yi, Taiwan;4. Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan;5. Department of Nursing, Tzu Hui Institute of Technology, Pingtung, Taiwan;6. Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan;7. Department of Rehabilitation, Kaohsiung Veterans General Hospital Tainan Branch, Tainan, Taiwan |
| |
| Abstract: | Tetramethylpyrazine (TMP) is a compound purified from herb. Its effect on Ca2+ concentrations (Ca2+]i) in renal cells is unclear. This study examined whether TMP altered Ca2+ signaling in Madin‐Darby canine kidney (MDCK) cells. TMP at 100–800 μM induced Ca2+]i rises, which were reduced by Ca2+ removal. TMP induced Mn2+ influx implicating Ca2+ entry. TMP‐induced Ca2+ entry was inhibited by 30% by modulators of protein kinase C (PKC) and store‐operated Ca2+ channels. Treatment with the endoplasmic reticulum Ca2+ pump inhibitor 2,5‐di‐tert‐butylhydroquinone (BHQ) inhibited 93% of TMP‐evoked Ca2+]i rises. Treatment with TMP abolished BHQ‐evoked Ca2+]i rises. Inhibition of phospholipase C (PLC) abolished TMP‐induced responses. TMP at 200–1000 μM decreased viability, which was not reversed by pretreatment with the Ca2+ chelator 1,2‐bis(2‐aminophenoxy)ethane‐N,N,N′,N′‐tetraacetic acid‐acetoxymethyl ester. Together, in MDCK cells, TMP induced Ca2+]i rises by evoking PLC‐dependent Ca2+ release from endoplasmic reticulum and Ca2+ entry via PKC‐sensitive store‐operated Ca2+ entry. TMP also caused Ca2+‐independent cell death. |
| |
| Keywords: | Ca2+ Cytotoxicity Renal tubular cells Tetramethylpyrazine |
|
|
