Molecular mechanisms of survival and apoptosis in RAW 264.7 macrophages under oxidative stress.
Organisms living in an aerobic environment are continuously exposed to reactive oxygen species (ROS). Apoptosis of cells can be induced by ROS and cells also develop negative feedback mechanisms to limit ROS induced cell death. In this study, RAW264.7 murine macrophage cells were treated with H(2)O(2) and cDNA microarray technique was used to produce gene expression profiles. We found that H(2)O(2) treatment caused up-regulation of stress, survival and apoptosis related genes, and down-regulation of growth and cell cycle promoting genes. Numerous genes of metabolism pathways showed special expression patterns under oxidative stress: glycolysis and lipid synthesis related genes were down-regulated whereas the genes of lipid catabolism and protein synthesis were up-regulated. We also identified several signaling molecules as ROS-responsive, including p53, Akt, NF-kappa B, ERK, JNK, p38, PKC and INF-gamma . They played important roles in the process of apoptosis or cell survival. Finally, an interactive pathway involved in cellular response to oxidative stress was proposed to provide some insight into the molecular events of apoptosis induced by ROS and the feedback mechanisms involved in cell survival.
Zhang
Y
Y
Department of Biology and Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong, People's Republic of China.
Fong
C C
CC
Wong
M S
MS
Tzang
C H
CH
Lai
W P
WP
Fong
W F
WF
Sui
S F
SF
Yang
M
M
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002402:Cathepsin D / Q000096:biosynthesis; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology*; D019926:Cyclin B / Q000096:biosynthesis; D015536:Down-Regulation; D015870:Gene Expression / Q000187:drug effects; D018841:HSP90 Heat-Shock Proteins / Q000096:biosynthesis; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008264:Macrophages / Q000502:physiology*; D008668:Metallothionein / Q000096:biosynthesis; D051379:Mice; D016328:NF-kappa B / Q000096:biosynthesis; D018384:Oxidative Stress / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D019926:Cyclin B; D018841:HSP90 Heat-Shock Proteins; C107835:Hspca protein, mouse; D016328:NF-kappa B; D016159:Tumor Suppressor Protein p53; D008668:Metallothionein; D006861:Hydrogen Peroxide; D002402:Cathepsin D