N-Nitrosodimethylamine induced lung fibroblast cell death is associated with JNK activation

被引:0
作者
Li, Bo [1 ,2 ]
Kim, Do-Sung [1 ]
Oh, Hyo-Won [3 ]
Lim, Hyun-Dae [4 ]
Lee, Wan [5 ]
Rhew, Ki Yon [6 ]
Kim, Hyung-Ryong [7 ,8 ]
Chae, Han-Jung [1 ,2 ]
机构
[1] Chonbuk Natl Univ, Sch Med, Dept Pharmacol, Jeonju, Chonbuk, South Korea
[2] Chonbuk Natl Univ, Sch Med, Inst Cardiovasc Res, Jeonju, Chonbuk, South Korea
[3] Wonkwang Univ, Sch Dent, Dept Publ Oral Hlth ancl Prevent Dent, Iksan, Chonbuk, South Korea
[4] Wonkwang Univ, Sch Dent, Dept Oral Med & Diag, Iksan, Chonbuk, South Korea
[5] Wonkwang Univ, Sch Dent, Dept Oral & Maxillofacial Radiol, Iksan, Chonbuk, South Korea
[6] Dongduk Womens Univ, Coll Pharm, Seoul, South Korea
[7] Wonkwang Univ, Dept Dent Pharmacol, Sch Dent, Iksan, Chonbuk, South Korea
[8] Wonkwang Univ, Sch Dent, Wonkwang Biomat Implant Res Inst, Iksan, Chonbuk, South Korea
关键词
N-nitrosodimethylamine; NDMA; JNK; ER stress; ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; INDUCED APOPTOSIS; ER STRESS; CYTOTOXICITY; EXPRESSION; INDUCTION; KINASES; MICE; LINE;
D O I
10.1007/s13273-012-0019-3
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
N-Nitrosodialkylamines are considered a potential health hazard for humans. Among various N-nitrosodialkylamines compound, N-nitrosodimethylamine (NDMA), was applied to lung cells, MLG. In order to examine the effect of NDMA in lung cells, cell death was first examined. NDMA induced cell death in a dose-dependent manner. Mitogen activated protein kinase (MAPK) involvement was tested using SP600125 for JNK, SB203580 for P38 MAPK, or PD98059 for ERK. SP compound induced a significant reduction of cell death, compared with other inhibitors. NDMA induced an increase in expression of ER stress response proteins, including GRP78, IRE-1 alpha, CHOP, GRP94, p-eIF2 alpha, p-JNK, or sXBP-1. Pretreatment with SP compound regulated expression of CHOP, the transcription factor associated with proapoptotic gene induction. This study showed that NDMA-induced cell death was resulted due to JNK activation. ER stress was also induced in the toxic situations. Study of the meaning of ER stress will be necessary in the near future.
引用
收藏
页码:155 / 161
页数:7
相关论文
共 42 条
[21]   Endoplasmic reticulum stress-mediated apoptosis in pancreatic β-cells [J].
Oyadomari, S ;
Araki, E ;
Mori, M .
APOPTOSIS, 2002, 7 (04) :335-345
[22]   DNA repair activity for oxidative damage and risk of lung cancer [J].
Paz-Elizur, T ;
Krupsky, M ;
Blumenstein, S ;
Elinger, D ;
Schechtman, E ;
Livneh, Z .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2003, 95 (17) :1312-1319
[23]  
Ramakrishna GT, 2000, MOL CARCINOGEN, V28, P156, DOI 10.1002/1098-2744(200007)28:3<156::AID-MC4>3.0.CO
[24]  
2-M
[25]   Effect of N-nitrosodimethylamine on inducible nitric oxide synthase expression and production of nitric oxide by neutrophils and mononuclear cells: the role of JNK signalling pathway [J].
Ratajczak-Wrona, Wioletta ;
Jablonska, Ewa ;
Garley, Marzena ;
Jablonski, Jakub ;
Radziwon, Piotr .
APMIS, 2011, 119 (07) :431-441
[26]   Correlation between induction of DNA fragmentation in lung cells from rats [J].
Robbiano, Luigi ;
Baroni, Debora ;
Novello, Luca ;
Brambilla, Giovanni .
MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS, 2006, 605 (1-2) :94-102
[27]   A trip to the ER: coping with stress [J].
Rutkowski, DT ;
Kaufman, RJ .
TRENDS IN CELL BIOLOGY, 2004, 14 (01) :20-28
[28]  
Schaeffer HJ, 1999, MOL CELL BIOL, V19, P2435
[29]   The mammalian unfolded protein response [J].
Schröder, M ;
Kaufman, RJ .
ANNUAL REVIEW OF BIOCHEMISTRY, 2005, 74 :739-789
[30]   DNA adducts, mutant frequencies and mutation spectra in λlacZ transgenic mice treated with N-nitrosodimethylamine [J].
Souliotis, VL ;
van Delft, JHM ;
Steenwinkel, MJST ;
Baan, RA ;
Kyrtopoulos, SA .
CARCINOGENESIS, 1998, 19 (05) :731-739