Prion infection correlates with hypersensitivity of P2X7 nucleotide receptor in a mouse microglial cell line.
We recently established mouse microglial cells persistently infected with mouse-adapted scrapie ME7 (ScMG20/ME7) for in vitro study of prion pathogenesis. Here, we found that ScMG20/ME7 cells were hypersensitive to P2X7 receptor agonists, as demonstrated by sustained Ca(2+) influx, membrane pore formation, cell death, and interleukin-1beta release. P2X7 mRNA expression was upregulated in these cells, and also in scrapie-infected mice brains. Treatment with pentosan polysulfate eliminated the infectivity and disease-related forms of prion protein from ScMG20/ME7 cell cultures, however, hypersensitivity of P2X7 receptors remained. These results suggest that prion infections may strongly affect the P2X7 receptor system in mouse microglial cells.
Takenouchi
Takato
T
Transgenic Animal Research Center, National Institute of Agrobiological Sciences, Ohwashi 1-2, Tsukuba, Ibaraki 305-8634, Japan.
Iwamaru
Yoshifumi
Y
Imamura
Morikazu
M
Kato
Nobuko
N
Sugama
Shuei
S
Fujita
Masayo
M
Hashimoto
Makoto
M
Sato
Mitsuru
M
Okada
Hiroyuki
H
Yokoyama
Takashi
T
Mohri
Shirou
S
Kitani
Hiroshi
H
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D051379:Mice; D008815:Mice, Inbred Strains; D017628:Microglia / Q000187:drug effects / Q000473:pathology*; D010426:Pentosan Sulfuric Polyester / Q000494:pharmacology; D011328:Prions / Q000472:pathogenicity*; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2 / Q000378:metabolism / Q000502:physiology; D058486:Receptors, Purinergic P2X7; D012608:Scrapie / Q000473:pathology*
C546469:P2rx7 protein, mouse; D011328:Prions; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D010426:Pentosan Sulfuric Polyester; C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; D000255:Adenosine Triphosphate