ᚑくᄢቇℂᎿቇ⎇ⓥႎ๔
J. Fac. Sci. Tech., Seikei Univ.
Vol.47 No.2 (2010) pp.35-36㧔⎇ⓥ⸳⟎⸳஻⚫੺࡮ႎ๔㧕✚ว↢๮⸃ᨆࠪࠬ࠹ࡓ  ᐕዉ౉ ߦࠃࠆ⎇ⓥᚑᨐ
ਭን ኼ*1


(Received September 21, 2010)㧞⮎೷ャㅍࠪࠬ࠹ࡓߣߒߡߩน⢻ᕈ

ߪߓ߼ߦ


ᰴߦ㜞ಽሶൻว‛ Poloxamer ߩ Drug Delivery 2007ᐕᐲߦ㈩஻ߐࠇߚ✚ว↢๮ࠪࠬ࠹ࡓߢߪ, ↢૕ౝ

System DDS ߳ ߩ ೑ ↪ ߩ น ⢻ ᕈ ࠍ ⺰ ߓ ߚ  ‫ޕ‬ߦ߅ߌࠆൻቇ‛⾰ߩ⋧੕ㅪ៤⸃ᨆࠍ⋡⊛ߣߒߡ㈩஻ߐࠇ

Poloxamer ߩ߁ߜ, Pluronic F68 ߣ Pluronic F127 ߣ๭߫ߚ‫ࡔ࠻ࠗࠨ࡯ࡠࡈࡦ࡚ࠪ࡯ࡘ࡝࠱࡟ࠗࡂߪࡓ࠹ࠬࠪᧄޕ‬࡯࠲࡯ Cell Lab Quanta SC (Beckman Coulter)߅ࠃ߮ABI

ࠇࠆ 2 ⒳㘃ߩ Poloxamer ߇⮎೷ᛩਈߩ㓙ߦ⮎‛ࠠࡖ࡝ࠕᚑ ߐ ࠇ , ߎ ࠇ ࠄ 㧞 ߟ ߩ ࡙ ࠾ ࠶ ࠻ ߦ ࠃ ࠅ DNA, mRNA,ߚ‫ޕ‬ታ㛎ߢߪ, Pluronic F68 ߪᘟᕈ㛽㜑ᕈ⊕ⴊ∛⚦⢩ᩣOmixࡌ࡯ࠬߩ⎇ⓥ߇น⢻ߣߥࠆ‫⎇߇ࡓ࠹ࠬࠪߩߎޕ‬ⓥߩ

NALM-6 ߩߺߦ, ࠕࡐ࠻࡯ࠪࠬࠍ⺃ዉߔࠆߎߣ߇᣿ࠄ

࡯ߣߒߡ೑↪น⢻ߢ޽ࠆ߆ࠍ, in vitro ߩታ㛎♽ߢ⏕⹺ߒ

PRISM 3130 Genetic Analyzer (Applied Biosystems)߆ࠄ᭴

K562 ߩߺߦ, Pluronic F127 ߪ B ⚦⢩⊕ⴊ∛⚦⢩ᩣProtein ࠍ⸃ᨆߔࠆ ߎ ߣ ߢ , ⋧ ਸ਼ ⊛ ߥ ࠺ ࡯ ࠲ ߇ ᓧ ࠄ ࠇ,ᔅ㗇࠷࡯࡞ߣߥࠆߩߪ㈩஻એ೨ࠃࠅᗐ௝ߒߡ޿ߚ‫⃻ޕ‬ታ߆ߣߥߞߚ‫ߩ‛⮎ޕ‬ᛩਈߢߪߥߊ, ⮎‛ࠠࡖ࡝ࠕ࡯ߩߺ

ߦ㈩஻એ㒠ߩᒰࠪࠬ࠹ࡓߦࠃࠅ, ᄙߊߩ⎇ⓥᚑᨐࠍ⺰ᢥߢࠕࡐ࠻࡯ࠪࠬ߇⺃ዉߐࠇࠆߚ߼, ߎࠇࠄ⚦⢩ᩣߢߪ⮎⊒⴫ߔࠆߦ⥋ߞߚ‫◲ࠍ߆ߟߊ޿ࠄ߆ߜ߁ߩࠄࠇߘޕ‬නߦ೷ߩലᨐ߇⋧ਸ਼⊛ߦ਄᣹ߔࠆߣ੍ᗐߐࠇߚ‫ࠄࠇߎޕ‬⚫੺ߒߚ޿‫ޕ‬

Poloxamer ߇৻ㇱߩ⊕ⴊ∛⚦⢩ᩣߦߩߺࠕࡐ࠻࡯ࠪࠬࠍ

⺃ዉߔࠆᯏᐨߪਇ᣿ߢ޽ࠆ߇, Pluronic F68 ߦࠃࠆ p53

ଐሽߩࠕࡐ࠻࡯ࠪࠬߪ⏕⹺ߒߡ޿ࠆ‫ޕ‬Poloxamer ߩ⮎‛㧝⌀ᕈ⿒ⴊ⃿Ⴧട∝ߦ߅ߌࠆㆮવሶᄌ⇣ߩหቯࠠࡖ࡝ࠕ࡯ߣߒߡߩ⹏ଔߪ߹ߛਇචಽߢ޽ࠆ߽ߩߩ,1 ߟ߼ߦ⚫੺ߔࠆߩߪJanus kinase 2 Jak2 ㆮવሶDDS ⎇ⓥߦ߅޿ߡ, න૕ߢ⮎ലࠍᜬߟ⮎‛ࠠࡖ࡝ࠕ࡯ߦ߅ߌࠆ৻Ⴎၮᄌ⇣ SNP ࠍ✂⟜⊛ߦ⸃ᨆߒ⌀ᕈ⿒ߣߒߡᦼᓙߐࠇࠆ‫ޕ‬ⴊ⃿Ⴧട∝ PV ᖚ⠪ߦ߅ߌࠆ․⇣⊛ߥㆮવሶᄌ⇣ࠍหቯߒߚߎߣߢ޽ࠆ  ‫⎇ޕ‬ⓥߢߪ33 ∝଀ߩ PV ᖚ⠪ߩⴊ㧟㉄ൻࠬ࠻࡟ࠬ㑐ㅪㆮવሶߩᄌ⇣૕ߩ⊒⷗ᶧ߆ࠄ DNA ࠍ᛽಴ߒ9p23 ਄ߩ Jak2 ㆮવሶߩ exon 12ᖚ⠪ߦߩߺ⏕⹺ߐࠇߚ‫ޕ‬ᄌ⇣ߪ 3 ⒳㘃ߩ SNP ߅ࠃ߮㧝߇⊒⃻ߐࠇࠆߣ⸘▚ߐࠇࠆ‫ޕ‬ᚒ‫ߩߎߪޘ‬ℂ⺰ߦၮߠ߈

㗔ၞߦ 4 ⒳㘃ߩᣂߚߥᄌ⇣ࠍหቯߒߚ‫ࠄࠇߎޕ‬ᄌ⇣ߪ PV

 1 ⒳㘃ߩㆮવሶ DNA ߆ࠄߪᐔဋߢ 3 ⒳㘃ߩ mRNA⒳㘃ߩᰳᄬߢ޽ࠅ, ޿ߕࠇ߽ Hot spot ਄ߦ⏕⹺ߐࠇߚ‫ޕ‬㉄ൻࠬ࠻࡟ࠬߦ㑐ㅪߔࠆ glutathione synthetase GSH࡜࠾ࡦߦᄌ⇣ߔࠆ V617F ᄌ⇣߇ᦨ߽㗫ᐲ߇㜞޿‫߆ߒޕ‬splicig variants ASVs ࠍ⊒⷗ߒߚ  ‫ޕ‬GSH ߩ ASVࠅ, ߘࠇࠄᖚ⠪ߦ߅޿ߡ, ⊒⷗ߒߚᄌ⇣ߪㆮવሶ⸻ᢿߣࠍᰳᄬߔࠆ߽ߩߢ޽ߞߚ‫ޕ‬ᚒ‫ߪޘ‬GSH ߿ GSR ߩ ASVPV ᖚ⠪ߦ߅޿ߡߪ, exon 11 㗔ၞߩࡃ࡝ࡦ߇ࡈࠚ࠾࡞ࠕ
ߒ, V617F ᄌ⇣߇ߥ޿ PV ᖚ⠪߽ዋᢙߥ߇ࠄሽ࿷ߒߡ߅

ߪ exon 4 ࠍGSR ߩ ASV ߪ exon 8 ޽ࠆ޿ߪ exon 9ߒߡᔕ↪น⢻ߢ޽ࠈ߁‫ߚ߹ޕ‬, V617F ᄌ⇣એᄖߦ㧞⒳㘃

ߩઁߦ߽ gamma-glutamylcysteine synthetase (GCLC)(rs10974944, rs12343867)ߩ SNP ߇ PV ᖚ⠪ߦ․⇣⊛ߢߩ ASV ߽⊒⷗ߒߡ߅ࠅ㉄ൻࠬ࠻࡟ࠬ㑐ㅪㆮવሶߦ߅

޽ࠆߣߩႎ๔߇޽ࠆ߇, ᣣᧄੱߦ߅޿ߡᦝߦ․⇣ᕈߩ㜞
޿ SNP ࠍ⊒⷗ߒߡ޿ࠆ(ᧂ⊒⴫࠺࡯࠲)‫⃻ߦࠄߐޕ‬࿷ᧄᘒᕈⴊዊ᧼ⴊ∝ ET ߦ߅޿ߡ߽ห᭽ߩ⸃ᨆࠍⴕߞߡ޿ࠆ‫ޕ‬㧦‛⾰↢๮ℂᎿቇ⑼ᢎ᝼ (hisatomi@st.seikei.ac.jp)

1߅ ࠃ ߮  glutathione reductase GSR ߩ alternative

ߌࠆ ASV ߩ⊒⷗߇⋧ᰴ޿ߢ޿ࠆ‫ ࠄࠇߎޕ‬ASVs ߪ⊹⤏⢄⤳⢗ߥߤߦ᥉ㆉ⊛ߦሽ࿷ߒߘߩ⊒⃻㊂ߪቢో㐳ߩ mRNA ㊂ߦଐሽߒߡ޿ࠆࠃ߁ߦ⷗߃ࠆ‫߼ߚߩߎޕ‬ᒰೋߪ dominant negative inhibitor ࠍ⠡⸶ߒߡ޿ࠆߣ⠨߃ߡ޿ߚ߇ߘࠇࠍุቯߔࠆታ㛎࠺࡯࠲߽಴ߡ߈ߡ޿ࠆ‫ޕ‬㧙㧙ߎࠇࠄ ASVs ߇නߥࠆ splicing error ߥߩ߆dominant

2. Aoki N, Tamura M, Ohyashiki JH, Sugaya M,⊛ߥ࠲ࡦࡄࠢ⾰ࠍ⠡⸶ߒߡ޿ࠆߩ߆ߪ⸃ᨆਛߢ޽ࠆ‫ޕ‬

human leukemia cell line. Molecular Medicine

negative inhibitor ߣߒߡ⠡⸶ߐࠇࠆߩ߆, ޽ࠆ޿ߪᯏ⢻Hisatomi H: Poloxamer 188 enhances apoptosis in aReports 3, 669-672, 2010.

߹ߣ߼

3.↰᧛୶ሶ,⩲⼱㤗Ꮧਭንኼ: Poloxamer 407 ߩࠕࡐ࠻࡯ࠪࠬ⺃ዉ⢻ߣ DDS ߣߒߡߩ᦭↪ᕈ. ᚑくᄢቇ ℂᎿቇ⎇ⓥႎ๔ 47, 27-31, 2010.

 ᧄࠪࠬ࠹ࡓߢᓧࠄࠇߚ⎇ⓥ࠺࡯࠲ߪ੹࿁⚫੺ߒߚ߽ߩએᄖߦ߽޿ߊߟ߆᜼ߍࠄࠇࠆ‫ޕ‬ዉ౉ᤨߦᣂ⊒ᄁߩᯏེ

4. Uchida M, Sugaya M, Kanamaru T, Hisatomi H:Alternative RNA splicing in expression of theߢ޽ߞߚߎߣ߆ࠄ߆ᯏེߩਇౕวߦᖠ߹ߐࠇߚᤨᦼ߽glutathione޽ߞߚ߇ዉ౉ᓟ⚂ 2 ᐕ⚻ㆊߒߚ੹ߢߪ໧㗴ߥߊⒿ௛ߒߡ޿ࠆ‫ޕ‬ዉ౉ߦࠃࠅDNA, mRNA, Protein ߇ࠃࠅ৻ጀᷓߊ⸃ᨆน⢻ߣߥߞߚߛߌߢߥߊ⸃ᨆߦ⥋ࠆ߹ߢߩ೨

synthetasegeneinhumancells.

Molecular Biology Reports 37, 2105-2109, 2010.

5. Satoh N, Watanabe N, Kanda A, Sugaya-Fukasawa
M, Hisatomi H: Expression of glutathione reductase

ಣℂࠍৼካߦᠲ૞ߔࠆߎߣߥߤߢ⎇ⓥቶߩታ㛎ᚻᛛ࡟

splice variants in human tissues. Biochemicalࡌ࡞߽ะ਄ߒߚߎߣࠍઃߌട߃ߡ߅ߊ‫ޕ‬

Genetics, 48, 816-821, 2010.

ᧄⓂߢ⚫੺ߒߚ⎇ⓥᚑᨐ

1. Ohyashiki JH, Hisatomi H, Shimizu S, Sugaya M,
Ohyashiki K: Detection of low allele burden ofJAK2 exon 12 mutations using TA-cloning inpatients with erythrocytosis. Japanese Journal of
Clinical Oncology 39, 509-513, 2010.
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