title: Arecoline induces TNF-alpha production and Zonula Occludens-1 redistribution in mouse Sertoli TM4 cells.
abstract: BACKGROUND
  Arecoline, a major alkaloid in Areca nut has the ability to induce oxidative stress. The effect of Areca nut, arecoline on reducing sperm quality and quantity were documented previously using several animal models. Junction disruption by down-regulation of the junction-adhesive protein via oxidative stress is an important route mediating abnormal spermatogenesis. Therefore, in this present study, we investigated the functional role of arecoline on junctional proteins.
  
  
  RESULTS
  To analyze direct effects of arecoline on testis cells, confluent mouse testicular Sertoli cell line TM4 was exposed to arecoline. Arecoline decreased insoluble zonula occludens-1 (ZO-1) protein expression in TM4 cells, however, arecoline treatment increased TNF-alpha production in both TM4 and monocytic THP1 cells. In addition, ERK1/2 inhibitor PD98059 reversed arecoline effects on TNF-alpha and ZO-1.
  
  
  CONCLUSIONS
  Arecoline increases the production of TNF-alpha and induces protein redistribution of ZO-1. All these results explain the role of arecoline in male reproductive dysfunction, besides its cytotoxic induction.
authors.forename: Tzer-Min
authors.initials: TM
authors.lastname: Kuo
authors.forename: Shun-Yuan
authors.initials: SY
authors.lastname: Luo
authors.forename: Shang-Lun
authors.initials: SL
authors.lastname: Chiang
authors.forename: Chi-Pin
authors.initials: CP
authors.lastname: Lee
authors.forename: Yu-Fan
authors.initials: YF
authors.lastname: Liu
authors.forename: Jan-Gowth
authors.initials: JG
authors.lastname: Chang
authors.forename: Ming-Hsui
authors.initials: MH
authors.lastname: Tsai
authors.affiliation: Environment-Omics-Disease Research Centre, China Medical University Hospital, Taichung, Taiwan. ycko0406@gmail.com.
authors.forename: Ying-Chin
authors.initials: YC
authors.lastname: Ko
mesh_terms: D000818:Animals; D001115:Arecoline / Q000009:adverse effects* / Q000494:pharmacology; D045744:Cell Line, Tumor; D018679:Cholinergic Agonists / Q000009:adverse effects* / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007248:Infertility, Male / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D012708:Sertoli Cells / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D062826:Zonula Occludens-1 Protein / Q000378:metabolism*
chemical_list: D018679:Cholinergic Agonists; D005419:Flavonoids; C569043:Tjp1 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D062826:Zonula Occludens-1 Protein; D001115:Arecoline; D048052:Mitogen-Activated Protein Kinase 3; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one