| Project/Area Number |
17390170
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Hygiene
|
|---|
| Research Institution | Mie University |
|---|
Principal Investigator |
OIKAWA Shinji Mie University, Graduate School of Medicine, Associate Professor (10277006)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MURATA Mariko Mie University, Graduate School of Medicine, Professor (10171141)
NOMURA Shinsuke Mie University, Graduate School of Medicine, Associate Professor (20198625)
FURUKAWA Ayako Institute for Developmental Ressarch, Aichi Human Service Center, Department of Pathology, Researcher (10455537)
|
|---|
| Project Period (FY) |
2005 – 2007
|
| Project Status |
Completed (Fiscal Year 2007)
|
| Budget Amount *help |
¥17,000,000 (Direct Cost: ¥15,200,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2007: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2006: ¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 2005: ¥3,200,000 (Direct Cost: ¥3,200,000)
|
|---|
| Keywords | reactive oxygen species / proteomics / oxidatively modified proteins / senescence acceleration / prevention / pathological aging / brain / oxidative stress / 老化 / プロフオシクス解析 / バイオマーカー / 慢性腎不全 / Hsp70 / 神経細胞死 / 記憶障害 / 老化促進モデルマウス / アルポートマウス / サル / 脳機能障害 / 高齢化 / 活性酸素種 / 機能プロテオミクス解析 / 老化のバイオマーカー |
|---|
| Research Abstract |
The reactive oxygen species(ROS), such as superoxide anion(O_2^-), hydrogen peroxide(H_2O_2) and free hydroxyl radicals(OH), participate in damage to cellular molecules including proteins. Recent studies suggest that abnormal protein oxidation may play an important role in acceleration of aging. In this study, we performed the identification and characterization of carbonyl-modified proteins, protein oxidation products, in hippocampal CAl region after transient cerebral ischemia-reperfusion using two-dimensional gel electrophoresis with immunochemical detection of protein carbonyls(2D Oxyblot). Ischemia-reperfusion induces the release of ROS, and organs are severely damaged by ischemia-reperfusion. Using 2D Oxyblot analysis, we demonstrated for the first time that carbonyl modification of Hsp70 in CA1 region was extensively increased prior to the neuronal cell death induced by ischemic-reperfusion insult. Hsp70 molecular chaperones are known to be induced by oxidative stress and have n
… More
europrotective function. Therefore, we considered that ischemia-reperfusion-induced oxidative damage to Hsp70 in CA1 region may lead to loss of the neuroprotective function, which contributes to neuronal cell death. In addition, we identified carbonyl modification proteins in liver and brain of SAMP8, which exhibits remarkable deficits in learning and memory, from peptide mass fingerprints using MALDI-TOF mass spectrometry in combination with LC-MS/MS analysis. Carbonyl modification of Cu,Zn-SOD in liver at 3 months and hippocampal cholinergic neurostimulating peptide precursor protein(HCNP-pp) in brain at 9 months were higher in SAMP8 compared with control SAMR1. We concluded that progressive accumulation of oxidative damage to Cu,Zn-SOD, may cause dysfunction of defense systems against oxidative stress in SAMP8 with a higher oxidative states, leading to acceleration of aging. Therefore, the generation of drugs sharing both antioxidant and carbonyl scavenger properties represents a new therapeutic challenge in the treatment of oxidative stress-associated diseases. Less
|
