Transient receptor potential melastatin type 7 channels are involved in zinc-induced apoptosis in gastric cancer

다국어 초록 (Multilingual Abstract)

Transient receptor potential melastatin 7 (TRPM7) channels are novel Ca^(2+)-permeable non-selective cation channels that are ubiquitously expressed. Activation of TRPM7 channels has been shown to be involved in the survival of gastric cancer cells. Here we show evidence suggesting that TRPM7 channels play an important role in Zn^(2+)-mediated cellular injury. Using a combination of electrophysiology, pharmacological analysis, small interfering RNA (siRNA) methods and cell death assays, we showed that activation of TRPM7 channels augmented Zn^(2+)-induced apoptosis of AGS cells, the most common human gastric adenocarcinoma cell line. The Zn^(2+)-mediated cytotoxicity was inhibited by the non-specific TRPM7 blockers Gd^(3+) or 2 aminoethoxydiphenyl borate (2-APB) and TRPM7 specific siRNA. In addition, we showed that overexpression of TRPM7 channels in HEK293 cells increased Zn^(2+)-induced cell injury. Thus, TRPM7 channels may represent a novel target for physiological disorders where Zn^(2+) toxicity plays an important role.

참고문헌 (Reference)

1 McLaughlin B, "p38 activation is required upstream of potassium current enhancement and caspase cleavage in thiol oxidant-induced neuronal apoptosis" 21 : 3303-3311, 2001

2 Brown AM, "Zn2 inhibits alpha-ketoglutarate-stimulated mitochondrial respiration and the isolated alpha-ketoglutarate dehydrogenase complex" 275 : 13441-13447, 2000

3 Kim YH, "Zincinduced cortical neuronal death with features of apoptosis and necrosis: mediation by free radicals" 89 : 175-182, 1999

4 Bitanihirwe BK, "Zinc: the brain’s dark horse" 63 : 1029-1049, 2009

5 Inoue K, "Zinc-induced neurotoxicity mediated by transient receptor potential melastatin 7 channels" 5 : 7430-7439, 2010

6 Sheline CT, "Zinc-induced cortical neuronal death: contribution of energy failure attributable to loss of NAD( ) and inhibition of glycolysis" 20 : 3139-3146, 2000

7 Formigari A, "Zinc, antioxidant systems and metallothionein in metal mediated-apoptosis: biochemical and cytochemical aspects" 146 : 443-459, 2007

8 Cuajungco MP, "Zinc metabolism in the brain: relevance to human neurodegenerative disorders" 4 : 137-169, 1997

9 Haase H, "Zinc induces apoptosis that can be suppressed by lanthanum in C6 rat glioma cells" 382 : 1228-1234, 2001

10 Watanabe T, "Zinc deficiency delays gastric ulcer healing in rats" 40 : 1340-1344, 1995

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

12 Berridge MJ, "The versatility and universality of calcium signaling" 1 : 11-21, 2000

13 Cummings JE, "The ubiquitous role of zinc in health and disease" 19 : 215-240, 2009

14 서상원, "The role of zinc in selective neuronal death after transient global cerebral ischemia" AMER ASSOC ADVANCEMENT SCIENCE 272 (272): 1013-1016, 199605

15 Truong-Tran AQ, "The role of zinc in caspase activation and apoptotic cell death" 14 : 315-330, 2001

16 Troskot B, "The protective effect of zinc sulphate pretreatment against duodenal ulcers in the rat" 10 : 325-329, 1997

17 Frederickson CJ, "The neurobiology of zinc in health and disease" 6 : 449-462, 2005

18 이은정, "The modulation of TRPV4 channel activity through its Ser 824 residue phosphorylation by SGK1" 한국통합생물학회 14 (14): 99-114, 2010

19 Feng P, "The involvement of Bax in zinc-induced mitochondrial apoptogenesis in malignant prostate cells" 7 : 25-, 2008

20 Vallee BL, "The biochemical basis of zinc physiology" 73 : 79-118, 1993

21 Monteilh-Zoller MK, "TRPM7 provides an ion channel mechanism for cellular entry of trace metal ions" 121 : 49-60, 2003

22 Runnels LW, "TRP-PLIK, a bifunctional protein with kinase and ion channel activities" 291 : 1043-1047, 2001

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

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

25 Bandyopadhyay B, "Serum zinc level: a possible index in the pathogenesis of peptic ulcer syndrome" 36 : 965-972, 1995

26 Kadakia SC, "Serum and tissue zinc concentrations in patients with endoscopic esophagitis" 37 : 513-516, 1992

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

28 Romani AM, "Regulation of cellular magnesium" 5 : D720-D734, 2000

29 Bandyopadhyay B, "Protective effect of zinc gluconate on chemically induced gastric ulcer" 106 : 27-32, 1997

30 Tagliati CA, "Pharmacokinetic profile and adverse gastric effect of zinc-piroxicam in rats" 33 : 67-71, 1999

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

32 Lichten LA, "Mammalian zinc transporters: nutritional and physiologic regulation" 29 : 153-176, 2009

33 Sempe´rtegui F, "Low concentrations of zinc in gastric mucosa are associated with increased severity of Helicobacter pylori-induced inflammation" 12 : 43-48, 2007

34 Calderone A, "Late calcium EDTA rescues hippocampal CA1 neurons from global ischemia-induced death" 24 : 9903-9913, 2004

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

36 Wastney ME, "Kinetic analysis of zinc metabolism and its regulation in normal humans" 251 : R398-R408, 1986

37 Volpe P, "Intracellular magnesium and inositol 1,4,5-trisphosphate receptor: molecular mechanisms of interaction, physiology and pharmacology" 6 : 267-274, 1993

38 Watjen W, "Induction of apoptosis in mammalian cells by cadmium and zinc" 110 : 865-867, 2002

39 Beyersmann D, "Functions of zinc in signaling, proliferation and differentiation of mammalian cells" 14 : 331-341, 2001

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

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

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

43 Cho CH, "Effect of zinc sulphate on ethanol- and indomethacin-induced ulceration and changes in prostaglandin E2 histaine levels in the rat gastric glandular mucosa" 32 : 288-295, 1985

44 Mann NS, "Effect of zinc sulfate and acetylcysteine on experimental gastric ulcer: in vitro study" 53 : 108-113, 1992

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

46 Lu HD, "Comparison of serum Zn,Cu and Se contents between healthy people and patients in high,middle and low incidence areas of gastric cancer of Fujian Province.World J Gastroenterol.5:84 86" 5 : 84-86, 1999

47 Choi DW, "Calcium-mediated neurotoxicity: relationship to specific channel types and role in ischemic damage" 11 : 465-469, 1988

48 Santos LH, "Anti-inflammatory, antinociceptive and ulcerogenic activity of a zinc-diclofenac complex in rats, In Anti-inflammatory, antinociceptive and ulcerogenic activity of a zinc-diclofenac complex in rats" 37 : 1205-1213, 2004

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