GART mediates the renewal of intestinal epithelial barrier via p38/p53/PUMA cascade in colitis

被引：9
|
作者：
Bai, Jian-an [1 ]
jie, Hua [2 ]
Wei, Sun [2 ]
Wang, Shidong [3 ]
Guo, Huarui [3 ]
Tang, Qiyun [2 ]
机构：
[1] Nanjing Med Univ, Sir Run Run Hosp, 109 Longmian Rd, Nanjing, Jiangsu, Peoples R China
[2] Nanjing Med Univ, Affiliated Hosp 1, 300 Guangzhou Rd, Nanjing NO300, Jiangsu, Peoples R China
[3] Linyi Cty Peoples Hosp, Dezhou, Shandong, Peoples R China
来源：
APOPTOSIS | 2016年 / 21卷 / 12期
基金：
中国国家自然科学基金;
关键词：
Apoptosis; Glycinamide ribonucleotide formyltransferase; Crohn's disease; Intestinal epithelial cells; P38; P53; INFLAMMATORY-BOWEL-DISEASE; GLYCINAMIDE RIBONUCLEOTIDE TRANSFORMYLASE; CROHNS-DISEASE; ANIMAL-MODELS; MANAGEMENT; APOPTOSIS; CELLS; PHOSPHORYLATION; PROLIFERATION; ACTIVATION;
D O I：
10.1007/s10495-016-1301-y
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Glycinamide ribonucleotide formyltransferase (GART) has been established as a pivotal enzyme in de novo purine synthesis, and mediates cellular apoptosis in many diseases. We aimed to investigate the role of GART in the pathogenesis of Crohn's disease (CD). In our study, we demonstrated for the first time that GART expression is up-regulated in patients with active CD and in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced acute colitis model. Moreover, the inhibition of GART induced cellular apoptosis and suppressed the migration of IECs through the activation of the MEKK3-MKK3-p38 mitogen-activated protein kinase (MAPK) pathway, following with the dys-regulation of p53 and p53 up-regulated modulator of apoptosis (PUMA). Taken together, GART plays a critical role in the protection of cellular apoptosis and migration of intestinal epithelial cells to maintain the integrity of the epithelial barrier, thus providing a new potential approach in designing a novel therapy for CD.
引用
收藏
页码：1386 / 1397
页数：12
相关论文
共 50 条
  • [21] Sulforaphane-induced apoptosis involves p53 and p38 in melanoma cells
    Rudolf, K.
    Cervinka, M.
    Rudolf, E.
    APOPTOSIS, 2014, 19 (04) : 734 - 747
  • [22] Sulforaphane-induced apoptosis involves p53 and p38 in melanoma cells
    K. Rudolf
    M. Cervinka
    E. Rudolf
    Apoptosis, 2014, 19 : 734 - 747
  • [23] Intestinal epithelial cell apoptosis requires BAX activation via p38 MAP kinase
    Sheng, George
    Warner, Brad
    JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS, 2006, 203 (03) : S49 - S49
  • [24] The JNK/P38 signalling pathway activated by testin protects the intestinal epithelial barrier against Crohn's disease-like colitis
    Song, Xue
    Zhang, Xiaofeng
    Zhang, Min
    Liu, Shengbao
    Zhang, Nuo
    Liu, Xinyue
    Li, Bohan
    Li, Jing
    Geng, Zhijun
    Zuo, Lugen
    Wang, Yueyue
    Wang, Lian
    Hu, Jianguo
    CHEMICO-BIOLOGICAL INTERACTIONS, 2024, 403
  • [25] LZAP Inhibits p38 MAPK (p38) Phosphorylation and Activity by Facilitating p38 Association with the Wild-Type p53 Induced Phosphatase 1 (WIP1)
    An, Hanbing
    Lu, Xinyuan
    Liu, Dan
    Yarbrough, Wendell G.
    PLOS ONE, 2011, 6 (01):
  • [26] RITA can induce cell death in p53-defective cells independently of p53 function via activation of JNK/SAPK and p38
    Weilbacher, A.
    Gutekunst, M.
    Oren, M.
    Aulitzky, W. E.
    van der Kuip, H.
    CELL DEATH & DISEASE, 2014, 5 : e1318 - e1318
  • [27] RITA can induce cell death in p53-defective cells independently of p53 function via activation of JNK/SAPK and p38
    A Weilbacher
    M Gutekunst
    M Oren
    W E Aulitzky
    H van der Kuip
    Cell Death & Disease, 2014, 5 : e1318 - e1318
  • [28] Zinc deficiency enhances p53 accumulation and phoshorylation by p38 kinase but alters p53 transactivation in HepG2 cells
    Cui, LB
    Wang, LR
    Alshatwi, A
    Schoene, NW
    Han, CT
    Fanzo, JC
    Lei, KY
    FASEB JOURNAL, 2004, 18 (04): : A102 - A103
  • [29] NRAGE mediates p38 activation and neural progenitor apoptosis via the bone morphogenetic protein signaling cascade
    Kendall, SE
    Battelli, C
    Irwin, S
    Mitchell, JG
    Glackin, CA
    Verdi, JM
    MOLECULAR AND CELLULAR BIOLOGY, 2005, 25 (17) : 7711 - 7724
  • [30] Hibiscus polyphenol-rich extract induces apoptosis in human gastric carcinoma cells via p53 phosphorylation and p38 MAPK/FasL cascade pathway
    Lin, HH
    Huang, HP
    Huang, CC
    Chen, JH
    Wang, CJ
    MOLECULAR CARCINOGENESIS, 2005, 43 (02) : 86 - 99
12345