NF-κB activation and susceptibility to apoptosis after polyamine depletion in intestinal epithelial cells

被引:92
|
作者
Li, L
Rao, JN
Bass, BL
Wang, JY
机构
[1] Baltimore Vet Affairs Med Ctr, Dept Surg, Baltimore, MD 21201 USA
[2] Univ Maryland, Sch Med, Dept Surg, Baltimore, MD 21201 USA
[3] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 2001年 / 280卷 / 05期
关键词
programmed cell death; ornithine decarboxylase; growth arrest; I kappa B; intestinal epithelium;
D O I
10.1152/ajpgi.2001.280.5.G992
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
The maintenance of intestinal mucosal integrity depends on a balance between cell renewal and cell death, including apoptosis. The natural polyamines, putrescine, spermidine, and spermine, are essential for mucosal growth, and decreasing polyamine levels cause G(1) phase growth arrest in intestinal epithelial (IEC-6) cells. The present study was done to determine changes in susceptibility of IEC-6 cells to apoptosis after depletion of cellular polyamines and to further elucidate the role of nuclear factor-kappaB (NF-kappaB) in this process. Although depletion of polyamines by alpha -difluoromethylornithine (DFMO) did not directly induce apoptosis, the susceptibility of polyamine-deficient cells to staurosporine (STS)-induced apoptosis increased significantly as measured by changes in morphological features and internucleosomal DNA fragmentation. In contrast, polyamine depletion by DFMO promoted resistance to apoptotic cell death induced by the combination of tumor necrosis factor-alpha (TNF-alpha) and cycloheximide. Depletion of cellular polyamines also increased the basal level of NF-kappaB proteins, induced NF-kappaB nuclear translocation, and activated the sequence-specific DNA binding activity. Inhibition of NF-kappaB binding activity by sulfasalazine or MG-132 not only prevented the increased susceptibility to STS-induced apoptosis but also blocked the resistance to cell death induced by TNF-alpha in combination with cycloheximide in polyamine-deficient cells. These results indicate that 1) polyamine depletion sensitizes intestinal epithelial cells to STS-induced apoptosis but promotes the resistance to TNF-alpha -induced cell death, 2) polyamine depletion induces NF-kappaB activation, and 3) disruption of NF-kappaB function is associated with altered susceptibility to apoptosis induced by STS or TNF-alpha. These findings suggest that increased NF-kappaB activity after polyamine depletion has a proapoptotic or antiapoptotic effect on intestinal epithelial cells determined by the nature of the death stimulus.
引用
收藏
页码:G992 / G1004
页数:13
相关论文
共 50 条
  • [21] NF-κB activation is required for apoptosis in fibrocystin/polyductin-depleted kidney epithelial cells
    Mangolini, Alessandra
    Bogo, Marco
    Durante, Chiara
    Borgatti, Monica
    Gambari, Roberto
    Harris, Peter C.
    Rizzuto, Rosario
    Pinton, Paolo
    Aguiari, Gianluca
    del Senno, Laura
    APOPTOSIS, 2010, 15 (01) : 94 - 104
  • [22] Polyamine depletion inhibits etoposide-induced NF-κB activation in transformed mouse fibroblasts
    Tantini, B
    Pignatti, C
    Fattori, M
    Fiumana, E
    Facchini, A
    Stefanelli, C
    Caldarera, CM
    Pegg, AE
    Flamigni, F
    AMINO ACIDS, 2004, 27 (02) : 207 - 214
  • [23] Polyamine depletion inhibits etoposide-induced NF-κB activation in transformed mouse fibroblasts
    B. Tantini
    C. Pignatti
    M. Fattori
    E. Fiumana
    A. Facchini
    C. Stefanelli
    C. M. Caldarera
    A. E. Pegg
    F. Flamigni
    Amino Acids, 2004, 27 : 207 - 214
  • [24] Significance of NF-κB activation in immortalization of nasopharyngeal epithelial cells
    Zhu, Dan Dan
    Zhang, Jun
    Deng, Wen
    Yip, Yim Ling
    Lung, Hong Lok
    Tsang, Chi Man
    Law, Wai Tak
    Yang, Jie
    Lau, Victoria Ming Yi
    Shuen, Wai Ho
    Lung, Maria Li
    Cheung, Annie Lai Man
    Tsao, Sai Wah
    INTERNATIONAL JOURNAL OF CANCER, 2016, 138 (05) : 1175 - 1185
  • [25] Activation of TGF-β-Smad signaling pathway following polyamine depletion in intestinal epithelial cells
    Liu, L
    Santora, R
    Rao, JN
    Guo, X
    Zou, TT
    Zhang, HFM
    Turner, DJ
    Wang, JY
    AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2003, 285 (05): : G1056 - G1067
  • [26] Cyclic-AMP mediated activation of NF-κB in intestinal epithelial cells:: Implications for cellular survival
    Rudolph, Jeffrey A.
    Pratt, Julia
    Steinbrecher, Kris A.
    Cohen, Mitchell B.
    GASTROENTEROLOGY, 2006, 130 (04) : A332 - A333
  • [27] Lithium induces NF-κB activation and interleukin-8 production in human intestinal epithelial cells
    Németh, ZH
    Deitch, EA
    Szabó, C
    Fekete, Z
    Hauser, CJ
    Haskó, G
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (10) : 7713 - 7719
  • [28] Glutamine prevents LPS-induced NF-κB activation in human intestinal epithelial cells.
    Moon, MR
    Pritts, TA
    Salzman, AL
    Fischer, JE
    Hasselgren, PO
    GASTROENTEROLOGY, 1998, 114 (04) : A1410 - A1411
  • [29] Induced Formation of Stress Granules Protects Intestinal Epithelial Cells Against Apoptosis Following Polyamine Depletion
    Zou, Tongtong
    Jiang, Zhengran
    Rao, Jaladanki N.
    Liu, Lan
    Xiao, Lan
    Yu, Tingxi
    Cui, Yu-hong
    Turner, Douglas J.
    Wang, Jian-Ying
    GASTROENTEROLOGY, 2010, 138 (05) : S401 - S401
  • [30] NF-κB activation mediated cellular death in lens epithelial cells after ultraviolet irradiation
    Cho, K
    Koh, C
    Lee, D
    Lee, J
    Joo, C
    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 1999, 40 (04) : S519 - S519