p66shc遺伝子の削除は,年齢に関連する内皮機能不全から保護します

Pietro Francia¹, Chiara delli Gatti, Markus Bachschmid

¹Cardiovascular Research & Cardiology, Institute of Physiology, Zürich, Irchel and University Hospital, Zürich, Switzerland.

Circulation

|October 27, 2004

まとめ

p66shcタンパク質が欠けているマウスは,年齢に関連する内皮機能障害と酸化ストレスに抵抗します. p66shcを非活性化すると,血管の老化から保護され,治療目標として提案されます.

科学分野:

血管生物学血管生物学
老化に関する研究
オキシダティブ・ストレスは,

背景:

活性酸素種 (ROS) の増産は,年齢に関連する内皮機能不全の重要な要因です.
p66shcタンパク質は,酸化ストレスに対する細胞の反応を調節する.
p66shcが欠けているマウスは,ROSに対する抵抗性が高まり,寿命が長くなります.

研究の目的:

p66shc遺伝子が欠けているマウスの内皮機能の年齢依存の変化を調査する.
老化中のROS媒介の内皮機能不全におけるp66shcの役割を決定する.

主な方法:

若年老齢のp66shc-/-および野生型 (WT) のマウスからの主動脈環のイソメトリック緊張記録.
ポルフィリン型マイクロセンサを用いた酸化窒素 (NO) 放出量の測定.
タンパク質発現 (eNOS,iNOS,スーパーオキシドディスミュータゼ) と,ウェスタン・ブロッティングと免疫ヒスト化学によるニトロチロシンの評価.
化学発光を用いた超酸化物 (O2-) 生成の決定.

主要な成果:

内皮に依存したリラクゼーションとNO放出は,WTマウスでは年齢によって低下したが,p66shc-/-マウスでは維持された.
古いWTマウスは,若いWTマウスと比較して,O2の生産とニトロチロシン発現の増加を示した.
老化はeNOSやマンガン超酸化物ディスミュータゼ発現に影響を与えなかったが,eNOSは古いWTマウスで上調された. これらの年齢による変化は,p66shc-/-マウスでは見られなかった.

結論:

p66shc遺伝子の不活性化は,年齢依存性,ROS媒介の内皮機能不全から保護する.
p66shcタンパク質は,内皮の完全性にとって重要な信号伝達経路に関与しています.
p66shcは,血管の老化を防ぐための新しい治療標的を代表する可能性があります.

さらに関連する動画

09:37

A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes Implicated in Human Diseases of Aging

Published on: July 14, 2016

07:04

Electroporation-Based Genetic Modification of Primary Human Pigment Epithelial Cells Using the Sleeping Beauty Transposon System

Published on: February 4, 2021

関連する概念動画

01:11

Genetic Lingo

Overview

01:33

Pleiotropy

Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...

02:18

Alternative RNA Splicing

Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...

02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...

01:20

Mismatch Repair

Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...

01:22

iPS Cell Differentiation

The ability of induced pluripotent stem cells or iPSCs to differentiate into most body cell types has stimulated repair and regenerative medicine research over the past few decades. iPSC-derived blood cells, hepatocytes, beta islet cells, cardiomyocytes, neurons, and other cell types can repair injuries or regenerate damaged tissue in diseases such as diabetes and neurodegenerative disorders.

関連する実験動画