|Budget Amount *help
¥2,300,000 (Direct Cost : ¥2,300,000)
Fiscal Year 1997 : ¥1,200,000 (Direct Cost : ¥1,200,000)
Fiscal Year 1996 : ¥1,100,000 (Direct Cost : ¥1,100,000)
The relationship between nitric oxide (NO) and cAMP in diabetic state
(1) using human neuroblastoma cell (SH-SY5Y)
We investigated the effect of ARI on NO production and cAMP formation in SH-SY5Y human neuroblastoma cells.
We measured nitrite and cGMP contents, cAMP contents and Na^+, K^+-ATPase activity in the presence of ARIs, ONO-2235 or SNK860, in the culture medium.
Both ARIs significantly reversed decreased nitrite and cGMP contents in a high glucose concentration. Both ARIs also significantly reversed decreased cAMP contents and impaired Na^+, K^+-ATPase activity in a high glucose concentration.
These data strongly suggest that the polyol pathway is involved in the mechanism by which a high glucose induces impaired NO production in SH-SY5Y cells and further that ARI may improve diabetic neuropathy at least in part by increasing nitric oxide production mediated by cAMP formation.
(2) using streptozotocin-induced diabetic rats
Nitrite contents, cGMP contents and cAMP contents were significantly reduced in the sciatic nerve of streptozotocin-induced rats during 6-12 weeks after streptozotocin injections. Based on these results, we are going to determine the change of nitrite contents, cGMP contents, Na^+, K^+-ATPase activity and nerve conduction velocity by administration of prostacyclin analog, dibuthyryl cAMP or ARIs.
The effect of glycation or free radical on NO production
(1) using SH-SY5Y
I have observed the change of nitrite and nitrate contents and cAMP levels by addition of SOD or aminoguanidine in media and cells, however, I have not gotten clear conclusion about it.
I will continue this basic study.