PMID- 24531690
OWN - NLM
STAT- MEDLINE
DCOM- 20140819
LR  - 20211021
IS  - 1523-1747 (Electronic)
IS  - 0022-202X (Linking)
VI  - 134
IP  - 7
DP  - 2014 Jul
TI  - Nonmetal haptens induce ATP release from keratinocytes through opening of 
      pannexin hemichannels by reactive oxygen species.
PG  - 1951-1960
LID - S0022-202X(15)36869-X [pii]
LID - 10.1038/jid.2014.93 [doi]
AB  - Although extracellular adenosine 5'-triphosphate (eATP) has a crucial role in the 
      sensitization phase of contact hypersensitivity (CHS), the mechanism by which 
      hapten causes keratinocyte cell death and ATP release is unknown. We examined the 
      time course of cell death, reactive oxygen species (ROS) production, and ATP 
      release in HaCaT cells and in normal human keratinocytes after exposure to 
      nonmetal haptens, NiCl2, or irritants. Both haptens and irritants caused cell 
      death of keratinocytes but with different time courses. N-acetylcysteine (NAC) 
      significantly reduced only nonmetal hapten-induced cell death as assessed by 
      propidium iodide exclusion. We examined the effects of antioxidants and pannexin 
      (Panx) inhibitors on cell death, ROS production, and ATP release by 
      chemical-treated HaCaT cells. Nonmetal hapten-induced cell death, but not NiCl2- 
      or irritant-related cell death, was dependent on reactivity to thiol residues in 
      the cells. NAC reduced cell death and ATP release, whereas antioxidants and Panx 
      inhibitors did not inhibit cell death but significantly attenuated ATP release. 
      Panx1 small interfering RNA (siRNA) also suppressed ATP release from 
      hapten-exposed HaCaT cells. Intraperitoneal injection of a Panx1 inhibitor 
      attenuated murine CHS. These findings suggest that nonmetal hapten reactivity to 
      thiol residues causes membrane disruption of keratinocytes and ROS production 
      that leads to ATP release through opening of Panx hemichannels.
FAU - Onami, Kaoru
AU  - Onami K
AD  - Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, 
      Japan.
FAU - Kimura, Yutaka
AU  - Kimura Y
AD  - Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, 
      Japan.
FAU - Ito, Yumiko
AU  - Ito Y
AD  - Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, 
      Japan.
FAU - Yamauchi, Takeshi
AU  - Yamauchi T
AD  - Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, 
      Japan.
FAU - Yamasaki, Kenshi
AU  - Yamasaki K
AD  - Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, 
      Japan.
FAU - Aiba, Setsuya
AU  - Aiba S
AD  - Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, 
      Japan. Electronic address: saiba@med.tohoku.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140214
PL  - United States
TA  - J Invest Dermatol
JT  - The Journal of investigative dermatology
JID - 0426720
RN  - 0 
      ((1,5-dihydro-5-(5-pyrimidine-2,4(1H,3H)-dionyl)-2H-chromeno(2,3-d)pyrimidine-2,4(3H)-dione))
RN  - 0 (Antioxidants)
RN  - 0 (Benzopyrans)
RN  - 0 (Connexins)
RN  - 0 (Dinitrochlorobenzene)
RN  - 0 (Haptens)
RN  - 0 (Irritants)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (PANX1 protein, human)
RN  - 0 (Pyrimidinones)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Reactive Oxygen Species)
RN  - 48TCX9A1VT (Cystine)
RN  - 696BNE976J (nickel chloride)
RN  - 7OV03QG267 (Nickel)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - YXO5V2CF3F (N-monoacetylcystine)
SB  - IM
MH  - Adenosine Triphosphate/*metabolism
MH  - Animals
MH  - Antioxidants/pharmacology
MH  - Benzopyrans/pharmacology
MH  - Cell Death/drug effects/physiology
MH  - Cells, Cultured
MH  - Connexins/chemistry/genetics/*metabolism
MH  - Cystine/analogs & derivatives/pharmacology
MH  - Dermatitis, Contact/*metabolism/pathology
MH  - Dinitrochlorobenzene/pharmacology
MH  - Disease Models, Animal
MH  - Female
MH  - Haptens/*metabolism
MH  - Humans
MH  - Irritants/pharmacology
MH  - Keratinocytes/cytology/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nerve Tissue Proteins/chemistry/genetics/*metabolism
MH  - Nickel/pharmacology
MH  - Protein Structure, Quaternary
MH  - Protein Structure, Tertiary
MH  - Pyrimidinones/pharmacology
MH  - RNA, Small Interfering/genetics
MH  - Reactive Oxygen Species/*metabolism
EDAT- 2014/02/18 06:00
MHDA- 2014/08/20 06:00
CRDT- 2014/02/18 06:00
PHST- 2013/09/26 00:00 [received]
PHST- 2014/01/30 00:00 [revised]
PHST- 2014/02/03 00:00 [accepted]
PHST- 2014/02/18 06:00 [entrez]
PHST- 2014/02/18 06:00 [pubmed]
PHST- 2014/08/20 06:00 [medline]
AID - S0022-202X(15)36869-X [pii]
AID - 10.1038/jid.2014.93 [doi]
PST - ppublish
SO  - J Invest Dermatol. 2014 Jul;134(7):1951-1960. doi: 10.1038/jid.2014.93. Epub 2014 
      Feb 14.