PMID- 29479036
OWN - NLM
STAT- MEDLINE
DCOM- 20180419
LR  - 20180419
IS  - 1880-3989 (Electronic)
IS  - 0388-1350 (Linking)
VI  - 43
IP  - 2
DP  - 2018
TI  - Arsenite exposure potentiates apoptosis-inducing effects of tumor necrosis 
      factor-alpha- through reactive oxygen species.
PG  - 159-169
LID - 10.2131/jts.43.159 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine released by 
      immune cells during inflammation process. Sodium arsenite (NaAsO(2)) is an 
      environmental toxic metal. The effects of excess NaAsO(2) on TNF-alpha response and 
      its intracellular signaling are not well understood. We hypothesized that 
      NaAsO(2) exposure might affect cellular response to TNF-alpha. Using HeLa cell model, 
      we found that the combination of NaAsO(2) and TNF-alpha clearly decreased cell 
      viability and mitochondrial membrane potential, but increased percentage of early 
      and late apoptotic cells and cleaved-poly (ADP-ribose) polymerase (PARP). 
      Moreover, the combination prolonged the phosphorylation of mitogen-activated 
      protein kinase (MAPK) members, including c-Jun-N-terminal kinase (JNK), p38, and 
      extracellular signal related kinases (ERK), and increased intracellular reactive 
      oxygen species (ROS), in comparison to treatment of NaAsO(2) or TNF-alpha alone. We 
      further investigated the role of ROS and MAPK signaling on this event by 
      inhibiting ROS production and MAPK. An antioxidant N-acetylcysteine pretreatment 
      diminished the apoptosis-inducing effect of NaAsO(2) and TNF-alpha combination and 
      also inhibited MAPK signaling. Using specific inhibitor of p38 (SB203580) and 
      siRNA-p38 surprisingly increased cell apoptosis and this effect was not observed 
      by JNK and ERK inhibition. This study suggests that p38 may possibly be a 
      survival mediator in response to environmental toxicant-related inflammation. In 
      conclusion, NaAsO(2) exposure might amplify inflammation-related tissue injury by 
      potentiating the apoptosis-inducing effect of TNF-alpha through ROS-dependent 
      mechanism.
FAU - Singhirunnusorn, Pattama
AU  - Singhirunnusorn P
AD  - Laboratory of Chemical Carcinogenesis, Chulabhorn Research Institute, Thailand.
FAU - Moolmuang, Benchamart
AU  - Moolmuang B
AD  - Laboratory of Chemical Carcinogenesis, Chulabhorn Research Institute, Thailand.
FAU - Lirdprapamongkol, Kriengsak
AU  - Lirdprapamongkol K
AD  - Laboratory of Biochemistry, Chulabhorn Research Institute, Thailand.
FAU - Ruchirawat, Mathuros
AU  - Ruchirawat M
AD  - Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Thailand.
LA  - eng
PT  - Journal Article
PL  - Japan
TA  - J Toxicol Sci
JT  - The Journal of toxicological sciences
JID - 7805798
RN  - 0 (Arsenates)
RN  - 0 (Environmental Pollutants)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 7XO134LHLN (sodium arsenate)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Apoptosis/*drug effects/physiology
MH  - Arsenates/*pharmacology
MH  - Cell Survival/drug effects
MH  - Environmental Pollutants/*pharmacology
MH  - HeLa Cells
MH  - Humans
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Phosphorylation/drug effects
MH  - Reactive Oxygen Species/*metabolism
MH  - Tumor Necrosis Factor-alpha/*metabolism/*pharmacology
MH  - p38 Mitogen-Activated Protein Kinases/metabolism/physiology
OTO - NOTNLM
OT  - Apoptosis
OT  - MAPK signaling pathway
OT  - Reactive oxygen species
OT  - Sodium arsenite (NaAsO2)
OT  - Tumor necrosis factor-alpha (TNF-alpha)
EDAT- 2018/02/27 06:00
MHDA- 2018/04/20 06:00
CRDT- 2018/02/27 06:00
PHST- 2018/02/27 06:00 [entrez]
PHST- 2018/02/27 06:00 [pubmed]
PHST- 2018/04/20 06:00 [medline]
AID - 10.2131/jts.43.159 [doi]
PST - ppublish
SO  - J Toxicol Sci. 2018;43(2):159-169. doi: 10.2131/jts.43.159.