117
118
Suramin による阻害効果を ATPγS（100 μM , P2Y 受容体アゴニスト sigma : A1388）を用いて確認した（Fig. 8-3~4）．ControlではATPγSを負荷することで細 胞内Ca2+の増加（蛍光の減少）とPKCαの変化が確認された．Suraminによって 阻害した条件ではATPγSを負荷してもCa2+とPKCαの蛍光は変化しなかった．
このことから，suraminによるATP受容体（GPCR）の阻害確認ができた．
Fig. 8-3 ATPγS負荷 Control， 上段：Ca2+，下段：PKCα
119
Fig. 8-4 ATPγS負荷 Suramin，上段：Ca2+，下段：PKCα
Thapsigargin負荷による細胞内小胞体からのCa2+の放出によるPKCαのト
ランスロケーション（Fig. 8-5）．細胞内Ca2+によってもPKCαのトランスロケ ーションを確認した．
Fig. 8-5 Thapsigargin負荷時のPKCαのトランスロケーション
120
FRAP 法を用いて 18α-GA と GAP27 の阻害効果を確認した．細胞は Calcein-AM（1 μM : 30分）を負荷し蛍光の指標にした．Bleaching時間は10分に設定 した（レーザー強度：30 ~ 40%）．Controlでは蛍光が回復していく様子が確認さ
れたが（Fig. 8-6），18α-GAとGAP27負荷時では蛍光の回復は観察されなかった
（Fig. 8-7 ~ 8）．このことから，18α-GAとGAP27によるGAP結合の阻害確認が できた．
Fig. 8-6 FRAP Control
Fig. 8-7 FRAP 18α-GA
Fig. 8-8 FRAP GAP27
121
Fig. 8-9各条件の輝度回復グラフ（n = 3）
122
焦点顕微鏡を用いて隣接細胞を創傷させたときの細胞内 Ca2+と PKCα-DG の 輝度変化を観察した．隣接細胞損傷後，細胞内 Ca2+濃度上昇と PKCα -DG が細 胞質から細胞膜へ移動していることが観察された（Fig. 8-10, 11）．×印は損傷さ せた細胞を示す．
Fig. 8-10 共焦点顕微鏡による細胞を創傷させたときのCa2+輝度変化
Fig. 8-11 共焦点顕微鏡による細胞を創傷させたときのPKCα-DG輝度変化
123
6 章の PKCα トランスロケーションの動態を改変したベイトマン方程式にフ ィッティングしPKCαの活性化と非活性化の反応速度定数を求めた．
Table. 8-1 The association （kon） and dissociation （koff） of initial and secondary translocations of PKCα. Data are averaged values ± S.E.
PKCα translocation at near membrane
PKCα translocation at far membrane
kon koff kon koff
Control 0.063 ± 0.006 0.063 ± 0.006 0.155 ± 0.011 0.167 ± 0.013
suramin 0.045 ± 0.007 0.046 ± 0.006 0.149 ± 0.033 0.181 ± 0.026
GAP27 0.053 ± 0.006 0.054 ± 0.006 0.138 ± 0.032 0.159 ± 0.030
18α-GA 0.121 ± 0.008 0.121 ± 0.008 0.185 ± 0.019 0.219 ± 0.017
Gd3+ 0.133 ± 0.011 0.174 ± 0.018
Removal of extracellular Ca2+
0.147 ± 0.014 0.171 ± 0.024
Inhibition of Ca2+
release from ER
0.070 ± 0.005 0.070 ± 0.005
124
第 6 章において細胞同士が接着していない状態で細胞を創傷したところ，周 辺細胞において Ca2+濃度上昇が起こることが確認されたが，周辺細胞内 PKCα の局在は観察されなかった．このことから第 4 章，第 6 章で観察されている隣 接細胞創傷による PKCα の局在は創傷によって漏れ出た細胞内溶液による反応 ではないと考えられる．創傷細胞と観察した細胞の距離は13.80 ± 2.01 μm．
Fig. 8-12 細胞間接着していない状態での細胞創傷時のPKCαとCa2+の輝度変化
（N=3，n =7 ）
125
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