Related Experiment Videos
Flavonoid-induced ability of minimally modified low-density lipoproteins to support lymphocyte proliferation
P Carrero1, H Ortega, J Martínez-Botas
1Servicio de Bioquímica-Investigación, Hospital Ramón y Cajal and Universidad de Alcalá de Henares, Madrid, Spain.
Abstract:
Low-density lipoprotein (LDL) peroxidation appears to be involved in atherogenesis. We studied the ability of minimally modified LDL (MM-LDL) to be used by proliferating lymphocytes and the effects of antioxidant flavonoids on this lipoprotein. MM-LDL were obtained by storing LDL at 4 degrees for 1 month, which resulted in a decrease in lipophilic antioxidants and an increased susceptibility to oxidation when incubated with cells. MM-LDL were not cytotoxic; however, in cells treated with lovastatin that require cholesterol for cell growth, they were much less efficient than fresh LDL in sustaining proliferation as determined by [3H]thymidine incorporation into DNA. Pure quercetin and grape-derived beverages restored proliferation in the presence of MM-LDL and prevented the apoptosis otherwise induced by lovastatin. These effects of flavonoids correlated with their activity in inhibiting LDL peroxidation. The results demonstrate that potent antioxidants, such as flavonoids, protect MM-LDL from lipoperoxidation and preserve their ability to efficiently deliver cholesterol to cells.
Insights
Antioxidant flavonoids protect minimally modified low-density lipoprotein (MM-LDL) from oxidation. This preserves MM-LDL's ability to deliver cholesterol, supporting cell proliferation and preventing apoptosis, crucial for understanding atherogenesis.
Area of Science:
- Cardiovascular Science
- Nutritional Biochemistry
- Cell Biology
Background:
- Low-density lipoprotein (LDL) peroxidation is implicated in atherogenesis.
- Minimally modified LDL (MM-LDL) exhibits reduced antioxidant content and increased susceptibility to oxidation.
- MM-LDL's role in cellular cholesterol delivery and proliferation requires further investigation.
Purpose of the Study:
- To investigate the utilization of MM-LDL by proliferating lymphocytes.
- To determine the effects of antioxidant flavonoids on MM-LDL and cellular processes.
- To assess the protective role of flavonoids against MM-LDL-induced cellular dysfunction.
Main Methods:
- Preparation of MM-LDL by prolonged LDL storage at 4°C.
- Assessment of MM-LDL's efficiency in sustaining lymphocyte proliferation via [3H]thymidine incorporation.
- Evaluation of pure quercetin and grape-derived beverages on MM-LDL-treated cells, including apoptosis assays.
- Correlation of flavonoid antioxidant activity with their effects on LDL peroxidation.
Main Results:
- MM-LDL was less efficient than fresh LDL in supporting proliferation of lovastatin-treated cells requiring cholesterol.
- Flavonoids (quercetin, grape beverages) restored proliferation and prevented lovastatin-induced apoptosis in the presence of MM-LDL.
- Flavonoid efficacy correlated with their inhibition of LDL peroxidation.
Conclusions:
- Potent antioxidants like flavonoids protect MM-LDL from lipoperoxidation.
- Flavonoids preserve the cholesterol-delivery function of MM-LDL, supporting cell growth.
- These findings highlight the atheroprotective potential of dietary antioxidants in modulating LDL metabolism.