PMID- 20200219
OWN - NLM
STAT- MEDLINE
DCOM- 20100810
LR  - 20220309
IS  - 1096-0929 (Electronic)
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 115
IP  - 2
DP  - 2010 Jun
TI  - Nickel sulfate induces location-dependent atrophy of mouse olfactory epithelium: 
      protective and proliferative role of purinergic receptor activation.
PG  - 547-56
LID - 10.1093/toxsci/kfq071 [doi]
AB  - Exposure to nickel sulfate (NiSO(4)) leads to impaired olfaction and anosmia 
      through an unknown mechanism. We tested the hypothesis that ATP is released 
      following NiSO4-induced injury and that ATP promotes regenerative cell 
      proliferation in the olfactory epithelium (OE). Male Swiss Webster mice were 
      intranasally instilled with NiSO(4) or saline followed by ATP, purinergic 
      receptor antagonists, or saline. We assessed the olfactory epithelium for 
      NiSO(4)-induced changes using histology and immunohistochemistry 1-7 days 
      postinstillation and compared results to olfactory bulb ablation-induced 
      toxicity. Intranasal instillation of NiSO(4) produced a dose- and time-dependent 
      reduction in the thickness of turbinate OE. These reductions were due to 
      sustentacular cell loss, measured by terminal dUTP nick-end labeling (TUNEL) 
      staining at 1-day postinstillation and caspase-3-dependent apoptosis of olfactory 
      sensory neurons at 3 days postinstillation. A significant increase in cell 
      proliferation was observed at 5 and 7 days postinstillation of NiSO(4) evidenced 
      by BrdU incorporation. Treatment with purinergic receptor antagonists 
      significantly reduced NiSO(4)-induced cell proliferation and posttreatment with 
      ATP significantly increased cell proliferation. Furthermore, posttreatment with 
      ATP had no effect on sustentacular cell viability but significantly reduced 
      caspase-3-dependent neuronal apoptosis. In a bulbectomy-induced model of 
      apoptosis, exogenous ATP produced a significant increase in cell proliferation 
      that was not affected by purinergic receptor antagonists, suggesting that ATP is 
      not released during bulbectomy-induced apoptosis. ATP is released following 
      NiSO(4)-induced apoptosis and has neuroproliferative and neuroprotective 
      functions. These data provide therapeutic strategies to alleviate or cure the 
      loss of olfactory function associated with exposure to nickel compounds.
FAU - Jia, Cuihong
AU  - Jia C
AD  - Department of Pharmacology and Toxicology, Michigan State University, East 
      Lansing, Michigan 48824, USA.
FAU - Roman, Carlos
AU  - Roman C
FAU - Hegg, Colleen C
AU  - Hegg CC
LA  - eng
GR  - R01 DC006897/DC/NIDCD NIH HHS/United States
GR  - 1R25NS065777/NS/NINDS NIH HHS/United States
GR  - DC006897/DC/NIDCD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100303
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Purinergic Antagonists)
RN  - 0 (Receptors, Purinergic)
RN  - 149017-66-3 (pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid)
RN  - 4FLT4T3WUN (nickel sulfate)
RN  - 5V5IOJ8338 (Pyridoxal Phosphate)
RN  - 6032D45BEM (Suramin)
RN  - 7OV03QG267 (Nickel)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
SB  - IM
MH  - Adenosine Triphosphate/metabolism/*pharmacology
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Atrophy/chemically induced/pathology
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Drug Therapy, Combination
MH  - Male
MH  - Mice
MH  - Nickel/*toxicity
MH  - Olfactory Bulb/drug effects/pathology/surgery
MH  - Olfactory Mucosa/*drug effects/pathology
MH  - Purinergic Antagonists
MH  - Pyridoxal Phosphate/analogs & derivatives/pharmacology
MH  - Receptors, Purinergic/*metabolism
MH  - Suramin/pharmacology
MH  - Turbinates/drug effects/pathology
PMC - PMC2871758
EDAT- 2010/03/05 06:00
MHDA- 2010/08/11 06:00
PMCR- 2011/06/01
CRDT- 2010/03/05 06:00
PHST- 2010/03/05 06:00 [entrez]
PHST- 2010/03/05 06:00 [pubmed]
PHST- 2010/08/11 06:00 [medline]
PHST- 2011/06/01 00:00 [pmc-release]
AID - kfq071 [pii]
AID - 10.1093/toxsci/kfq071 [doi]
PST - ppublish
SO  - Toxicol Sci. 2010 Jun;115(2):547-56. doi: 10.1093/toxsci/kfq071. Epub 2010 Mar 3.