Homocysteine-induced decrease in HUVEC cells' resistance to oxidative stress is mediated by Akt-dependent changes in...

Area of Science:

• Biochemistry
• Cell Biology
• Toxicology

Background:

• Hyperhomocysteinemia is a risk factor for cardiovascular and neurodegenerative diseases.
• Iron may mediate homocysteine (Hcy) toxicity.

Purpose of the Study:

• Investigate the effect of Hcy on iron metabolism in HUVEC and SH-SY5Y cells.
• Elucidate the molecular mechanisms underlying Hcy-induced changes in iron metabolism.

Main Methods:

• HUVEC and SH-SY5Y cells were treated with 3 mM Hcy.
• Analyzed ferritin expression, Akt kinase activity, and FOXO3a signaling.
• Utilized siRNA to investigate the roles of Akt and FOXO3a.

Main Results:

• Hcy upregulated ferritins L and H in HUVEC cells in a time-dependent manner.
• Hcy decreased active Akt kinase in HUVEC cells, preceding ferritin changes.
• Akt activation increased ferritin levels, while FOXO3a inhibition decreased them.
• Hcy-treated HUVEC cells showed increased hydrogen peroxide cytotoxicity.

Conclusions:

• Hcy increases cellular ferritin levels via the Akt-FOXO3a signaling pathway.
• This pathway modulation affects iron metabolism and cellular response to oxidative stress.