Proteomic identification of protein targets for 15-deoxy-Δ(12,14)-prostaglandin J2 in neuronal plasma membrane.
15-deoxy-Δ(12,14)-prostaglandin J(2) (15d-PGJ(2)) is one of factors contributed to the neurotoxicity of amyloid β (Aβ), a causative protein of Alzheimer's disease. Type 2 receptor for prostaglandin D(2) (DP2) and peroxysome-proliferator activated receptorγ (PPARγ) are identified as the membrane...
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oai:doaj.org-article:719813be86c243dab0ba9827cd7611982021-11-18T06:57:06ZProteomic identification of protein targets for 15-deoxy-Δ(12,14)-prostaglandin J2 in neuronal plasma membrane.1932-620310.1371/journal.pone.0017552https://doaj.org/article/719813be86c243dab0ba9827cd7611982011-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21445266/?tool=EBIhttps://doaj.org/toc/1932-620315-deoxy-Δ(12,14)-prostaglandin J(2) (15d-PGJ(2)) is one of factors contributed to the neurotoxicity of amyloid β (Aβ), a causative protein of Alzheimer's disease. Type 2 receptor for prostaglandin D(2) (DP2) and peroxysome-proliferator activated receptorγ (PPARγ) are identified as the membrane receptor and the nuclear receptor for 15d-PGJ(2), respectively. Previously, we reported that the cytotoxicity of 15d-PGJ(2) was independent of DP2 and PPARγ, and suggested that 15d-PGJ(2) induced apoptosis through the novel specific binding sites of 15d-PGJ(2) different from DP2 and PPARγ. To relate the cytotoxicity of 15d-PGJ(2) to amyloidoses, we performed binding assay [(3)H]15d-PGJ(2) and specified targets for 15d-PGJ(2) associated with cytotoxicity. In the various cell lines, there was a close correlation between the susceptibilities to 15d-PGJ(2) and fibrillar Aβ. Specific binding sites of [(3)H]15d-PGJ(2) were detected in rat cortical neurons and human bronchial smooth muscle cells. When the binding assay was performed in subcellular fractions of neurons, the specific binding sites of [(3)H]15d-PGJ(2) were detected in plasma membrane, nuclear and cytosol, but not in microsome. A proteomic approach was used to identify protein targets for 15d-PGJ(2) in the plasma membrane. By using biotinylated 15d-PGJ(2), eleven proteins were identified as biotin-positive spots and classified into three different functional proteins: glycolytic enzymes (Enolase2, pyruvate kinase M1 (PKM1) and glyceraldehyde 3-phosphate dehydrogenase (GAPDH)), molecular chaperones (heat shock protein 8 and T-complex protein 1 subunit α), cytoskeletal proteins (Actin β, F-actin-capping protein, Tubulin β and Internexin α). GAPDH, PKM1 and Tubulin β are Aβ-interacting proteins. Thus, the present study suggested that 15d-PGJ(2) plays an important role in amyloidoses not only in the central nervous system but also in the peripheral tissues.Yasuhiro YamamotoKenkichi TakaseJunji KishinoMegumi FujitaNoboru OkamuraToshiyuki SakaedaMasafumi FujimotoTatsurou YagamiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 3, p e17552 (2011) |
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Medicine R Science Q Yasuhiro Yamamoto Kenkichi Takase Junji Kishino Megumi Fujita Noboru Okamura Toshiyuki Sakaeda Masafumi Fujimoto Tatsurou Yagami Proteomic identification of protein targets for 15-deoxy-Δ(12,14)-prostaglandin J2 in neuronal plasma membrane. |
| description |
15-deoxy-Δ(12,14)-prostaglandin J(2) (15d-PGJ(2)) is one of factors contributed to the neurotoxicity of amyloid β (Aβ), a causative protein of Alzheimer's disease. Type 2 receptor for prostaglandin D(2) (DP2) and peroxysome-proliferator activated receptorγ (PPARγ) are identified as the membrane receptor and the nuclear receptor for 15d-PGJ(2), respectively. Previously, we reported that the cytotoxicity of 15d-PGJ(2) was independent of DP2 and PPARγ, and suggested that 15d-PGJ(2) induced apoptosis through the novel specific binding sites of 15d-PGJ(2) different from DP2 and PPARγ. To relate the cytotoxicity of 15d-PGJ(2) to amyloidoses, we performed binding assay [(3)H]15d-PGJ(2) and specified targets for 15d-PGJ(2) associated with cytotoxicity. In the various cell lines, there was a close correlation between the susceptibilities to 15d-PGJ(2) and fibrillar Aβ. Specific binding sites of [(3)H]15d-PGJ(2) were detected in rat cortical neurons and human bronchial smooth muscle cells. When the binding assay was performed in subcellular fractions of neurons, the specific binding sites of [(3)H]15d-PGJ(2) were detected in plasma membrane, nuclear and cytosol, but not in microsome. A proteomic approach was used to identify protein targets for 15d-PGJ(2) in the plasma membrane. By using biotinylated 15d-PGJ(2), eleven proteins were identified as biotin-positive spots and classified into three different functional proteins: glycolytic enzymes (Enolase2, pyruvate kinase M1 (PKM1) and glyceraldehyde 3-phosphate dehydrogenase (GAPDH)), molecular chaperones (heat shock protein 8 and T-complex protein 1 subunit α), cytoskeletal proteins (Actin β, F-actin-capping protein, Tubulin β and Internexin α). GAPDH, PKM1 and Tubulin β are Aβ-interacting proteins. Thus, the present study suggested that 15d-PGJ(2) plays an important role in amyloidoses not only in the central nervous system but also in the peripheral tissues. |
| format |
article |
| author |
Yasuhiro Yamamoto Kenkichi Takase Junji Kishino Megumi Fujita Noboru Okamura Toshiyuki Sakaeda Masafumi Fujimoto Tatsurou Yagami |
| author_facet |
Yasuhiro Yamamoto Kenkichi Takase Junji Kishino Megumi Fujita Noboru Okamura Toshiyuki Sakaeda Masafumi Fujimoto Tatsurou Yagami |
| author_sort |
Yasuhiro Yamamoto |
| title |
Proteomic identification of protein targets for 15-deoxy-Δ(12,14)-prostaglandin J2 in neuronal plasma membrane. |
| title_short |
Proteomic identification of protein targets for 15-deoxy-Δ(12,14)-prostaglandin J2 in neuronal plasma membrane. |
| title_full |
Proteomic identification of protein targets for 15-deoxy-Δ(12,14)-prostaglandin J2 in neuronal plasma membrane. |
| title_fullStr |
Proteomic identification of protein targets for 15-deoxy-Δ(12,14)-prostaglandin J2 in neuronal plasma membrane. |
| title_full_unstemmed |
Proteomic identification of protein targets for 15-deoxy-Δ(12,14)-prostaglandin J2 in neuronal plasma membrane. |
| title_sort |
proteomic identification of protein targets for 15-deoxy-δ(12,14)-prostaglandin j2 in neuronal plasma membrane. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2011 |
| url |
https://doaj.org/article/719813be86c243dab0ba9827cd761198 |
| work_keys_str_mv |
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