1 0 0 0 OA 尿毒症物質により誘発される心腎連関を介した酸化ストレス臓器障害の分子機構
- 著者
- 渡邊 博志
- 出版者
- 公益社団法人 日本薬学会
- 雑誌
- YAKUGAKU ZASSHI (ISSN:00316903)
- 巻号頁・発行日
- vol.133, no.8, pp.889-895, 2013-08-01 (Released:2013-08-01)
- 参考文献数
- 28
- 被引用文献数
- 4 6
Chronic kidney disease (CKD), marked by a progressive loss in renal function, is a leading cause of hemodialysis initiation and cardiovascular disease (CVD). There are currently 13.3 million patients with CKD and 300 thousand patients are currently undergoing hemodialysis in Japan. Therefore, preventing the initiation of dialysis and reducing the risk of cardiovascular death are high-priority issues from the viewpoint of public health and economic implications. Understanding the molecular mechanism responsible for the progression of CKD and cardiovascular damage regarding crosstalk between the kidney and cardiovascular system is an important issue in controlling the pathogenesis of CKD-CVD. However, the mechanisms involved in CKD-CVD are not well understood. This hinders the development of new treatment strategies. We have been investigating the role of protein bound uremic toxins, that are difficult to remove by hemodialysis, on the onset and progression of CKD and CVD. The relationship between their redox properties and the pathogenesis of CKD-CVD was examined. In this review, we focus on two sulfate conjugated uremic toxins, namely, indoxyl sulfate (IS) and p-cresyl sulfate (PCS), and summarize recent studies that provide new insights on the molecular mechanisms responsible for uremic toxin-induced oxidative tissue damage via a cardiovascular-renal connection.
1 0 0 0 OA 分子進化工学手法を駆使した毒素中和型アルブミンによるハイブリッド血液浄化法の開発
本研究では標的分子をBRに絞り込み、BR捕獲型HSAドメインの設計と新規BR除去療法としての有用性を評価するため、以下の検討を行った。得られた知見を要約する。(1)進化工学的手法であるファージディスプレイ法を駆使してBRの詳細な結合部位の同定を可能にし、さらに1.6×105個の変異体の中からBR高親和性HSAドメインII変異体を拾い上げることに成功した。(2)今回作製した新規BR尿中排泄促進剤pan3_3-13は、抗体製剤よりも製造コストが低く、従来の血液浄化法の基盤を成す血液透析に替わり、侵襲性の低い新たな血液浄化法の道を拓くことが大いに期待される。