The role of ginseng total saponin in transient receptor potential melastatin type 7 channels

다국어 초록 (Multilingual Abstract)

Although ginsenosides have a variety of physiologic or pharmacologic functions in various regions, there are only a few reports on the effects of transient receptor potential melastatin 7 (TRPM7) channels. Here, we showed evidence suggesting that TRPM7 channels play an important role in ginseng total saponin (GTS)-mediated cellular injury. The combination techniques of electrophysiology, pharmacological analysis, small interfering RNA (siRNA) method and cell death assays were used. GTS depolarized the resting membrane potentials and decreased the amplitude of pacemaker potentials in cultured interstitial cells of Cajal (ICCs) in gastrointestinal (GI) tract. The TRPM7-like currents in single ICCs and the overexpressing TRPM7 in HEK293 cells were inhibited by GTS. However, GTS had no effect on Ca2-activated Cl conductance. GTS inhibited the survival of human gastric (AGS) and breast (MCF-7) adenocarcinoma cells. Also, GTS inhibited the TRPM7-like currents in AGS and MCF-7 cells. The GTSmediated cytotoxicity was inhibited by TRPM7-specific siRNA. In addition, we showed that overexpression of TRPM7 channels in HEK293 cells was inhibited by GTS. Thus, TRPM7 channels are involved in GTS-mediated cell death in AGS and MCF-7 cells, and these channels may represent a novel target for physiological disorders where GTS plays an important role.

참고문헌 (Reference)

1 Sang-Min Jang, "p19ras Accelerates p73β-mediated Apoptosis through a Caspase-3 Dependent Pathway" 한국통합생물학회 13 (13): 399-403, 2009

2 Goto K, "Two types of spontaneous depolarizations in the interstitial cells freshly prepared from the murine small intestine" 559 : 411-422, 2004

3 Jiang J, "Transient receptor potential melastatin 7-like current in human head and neck carcinoma cells : role in cell proliferation" 67 : 10929-10938, 2007

4 Lee JH, "The effects of ginsenoside Rg(3) on human Kv1.4 channel currents without the N-terminal rapid inactivation domain" 32 : 614-618, 2009

5 Clapham DE, "TRP channels as cellular sensors" 426 : 517-524, 2003

6 Yang YD, "TMEM16A confers receptor-activated calcium-dependent chloride conductance" NATURE PUBLISHING GROUP 455 (455): 1210-36, 200810

7 Kim BJ, "Suppression of transient receptor potential melastatin 7 channel induces cell death in gastric cancer" 99 : 2502-2509, 2008

8 Koh SD, "Spontaneous electrical rhythmicity in cultured interstitial cells of cajal from the murine small intestine" 513 : 203-213, 1998

9 Schmitz C, "Regulation of vertebrate cellular Mg2+ homeostasis by TRPM7" 114 : 191-200, 2003

10 Faleiro L, "Multiple species of CPP32 and Mch2 are the major active caspases present in apoptotic cells" 16 : 2271-2281, 1997

11 Kim BJ, "Melastatin-type transient receptor potential channel 7 is required for intestinal pacemaking activity" W B SAUNDERS CO-ELSEVIER INC 129 : 1504-1517, 200511

12 Nadler MJ, "LTRPC7 is a Mg. ATP-regulated divalent cation channel required for cell viability" 411 : 590-595, 2001

13 임혜원, "Inhibitory effect of ginsenosides on NMDA receptor-mediated signals in rat hippocampal neurons" 296 : 247-254, 200208

14 Zhang Y, "Ginsenoside-Rd attenuates TRPM7 and ASIC1a but promotes ASIC2a expression in rats after focal cerebral ischemia" 2012

15 Sun-Hye Choi, "Ginsenoside Rg_3 Enhances Large Conductance Ca^(2+)-Activated Potassium Channel Currents: A Role of Tyr360 Residue" 한국분자세포생물학회 31 (31): 133-140, 2011

16 임혜원, "Ginsenoside Rg3 antagonizes NMDA receptors through a glycine modulatory site in rat cultured hippocampal neurons" 323 (323): 416-424, 200410

17 Choi SH, "Ginsenoside Rg3 activates human KCNQ1 K- channel currents through interacting with the K318 and V319 residues: a role of KCNE1 subunit" 637 : 138-147, 2010

18 최선혜, "Ginsenoside Rg(3) decelerates hERG K+ channel deactivation through Ser631 residue interaction" ELSEVIER SCIENCE BV 663 (663): 59-67, 201108

19 Attele AS, "Ginseng pharmacology : multiple constituents and multiple actions" 58 : 1685-1693, 1999

20 Rhim H, "Ginseng and ginsenoside Rg3, a newly identified active ingredient of ginseng, modulate Ca2+ channel currents in rat sensory neurons" 436 : 151-158, 2002

21 Nah SY, "Ginseng : recent advances and trends" 21 : 1-12, 1997

22 Wang BJ, "Free radical scavenging and apoptotic effects of cordycepin sinensis ractionated by supercritical carbon dioxide" 43 : 543-552, 2005

23 Vermes I, "Flow cytometry of apoptotic cell death" 243 : 167-190, 2000

24 Hotz MA, "Flow cytometric detection of apoptosis : comparison of the assays of in situ DNA degradation and chromatin changes" 15 : 237-244, 1994

25 Hwang SJ, "Expression of anoctamin 1/TMEM16A by interstitial cells of Cajal is fundamental for slow wave activity in gastrointestinal muscles" 587 : 4887-4904, 2009

26 Schroeder BC, "Expression cloning of TMEM16A as a calcium-activated chloride channel subunit" 134 : 1019-1029, 2008

27 Guilbert A, "Evidence that TRPM7 is required for breast cancer cell proliferation" 297 : 493-502, 2009

28 성현환, "Effects of ginsenoside on large-conductance K(Ca) channels in human corporal smooth muscle cells" NATURE PUBLISHING GROUP 23 : 193-199, 201109

29 Jin J, "Deletion of Trpm7 disrupts embryonic development and thymopoiesis without altering Mg2+ homeostasis" 322 : 756-760, 2008

30 Gomez-Pinilla PJ, "Ano1 is a selective marker of interstitial cells of Cajal in the human and mouse gastrointestinal tract" 296 : 1370-1381, 2009

31 Nicoletti I, "A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry" 139 : 271-279, 1991

32 Kang SJ, "A possible physiological role of caspase-11 during germinal center reaction" 12 : 127-136, 2008

33 Zhu MH, "A Ca(2+)-activated Cl(-)conductance in interstitial cells of Cajal linked to slow wave currents and pacemaker activity" 587 : 4905-4982, 2009