Critical involvement of extracellular ATP acting on P2RX7 purinergic receptors in photoreceptor cell death

Shoji Notomi, Toshio Hisatomi, Takaaki Kanemaru, Atsunobu Takeda, Yasuhiro Ikeda, Hiroshi Enaida, Guido Kroemer, Tatsuro Ishibashi

研究成果: Contribution to journalArticle査読

58 被引用数 (Scopus)

抄録

Stressed cells release ATP, which participates in neurodegenerative processes through the specific ligation of P2RX7 purinergic receptors. Here, we demonstrate that extracellular ATP and the more specific P2RX7 agonist, 2′- and 3′-O-(4-benzoylbenzoyl)-ATP, both induce photoreceptor cell death when added to primary retinal cell cultures or when injected into the eyes from wild-type mice, but not into the eyes from P2RX7-/- mice. Photoreceptor cell death was accompanied by the activation of caspase-8 and -9, translocation of apoptosis-inducing factor from mitochondria to nuclei, and TUNEL-detectable chromatin fragmentation. All hallmarks of photoreceptor apoptosis were prevented by premedication or co-application of Brilliant Blue G, a selective P2RX7 antagonist that is already approved for the staining of internal limiting membranes during ocular surgery. ATP release is up-regulated by nutrient starvation in primary retinal cell cultures and seems to be an initializing event that triggers primary and/or secondary cell death via the positive feedback loop on P2RX7. Our results encourage the potential application of Brilliant Blue G as a novel neuroprotective agent in retinal diseases or similar neurodegenerative pathologies linked to excessive extracellular ATP.

本文言語英語
ページ(範囲)2798-2809
ページ数12
ジャーナルAmerican Journal of Pathology
179
6
DOI
出版ステータス出版済み - 12 2011

All Science Journal Classification (ASJC) codes

  • 病理学および法医学

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