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Published on: July 20, 2019
Cyp1B1 expression promotes angiogenesis by suppressing NF-κB activity
Tammy L Palenski1, Zafer Gurel, Christine M Sorenson
1Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin;
American Journal of Physiology. Cell Physiology
|October 4, 2013
Summary
Cytochrome P-450 1B1 (Cyp1B1) deficiency in vascular cells increases oxidative stress and NF-κB activation, linked to thrombospondin-2 (TSP2). Antioxidants PEITC and PDTC partially restore cell function by inhibiting NF-κB.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Nuclear factor-κB (NF-κB) regulates angiogenesis and inflammation.
- Cytochrome P-450 1B1 (Cyp1B1) deficiency in vascular cells increases oxidative stress, impairs migration and capillary morphogenesis, activates NF-κB, and upregulates thrombospondin-2 (TSP2).
Purpose of the Study:
- To investigate the therapeutic potential of antioxidants phenethyl isothiocyanate (PEITC) and pyrrolidine dithiocarbamate (PDTC) in restoring normal vascular cell phenotype.
- To elucidate the role of TSP2 in NF-κB activity and angiogenesis in the context of Cyp1B1 deficiency.
Main Methods:
- Treatment of Cyp1B1-deficient (cyp1b1(-/-)) endothelial cells (EC) and pericytes (PC) with PEITC and PDTC.
- Assessment of NF-κB activity, oxidative stress, cell migration, and capillary morphogenesis.
- Manipulation of TSP2 and inhibitor κBα (IκBα) expression levels.
Main Results:
- PEITC and PDTC inhibited NF-κB activity and expression in cyp1b1(-/-) EC and PC.
- These antioxidants restored EC migration and capillary morphogenesis and decreased oxidative stress.
- TSP2 expression modulated NF-κB activity, with TSP2 knockdown attenuating NF-κB activity in cyp1b1(-/-) cells and TSP2 overexpression increasing NF-κB activity in wild-type cells.
Conclusions:
- Cyp1B1 expression in vascular cells is crucial for maintaining vascular homeostasis.
- Cyp1B1 regulates cellular redox state, TSP2 expression, and NF-κB activation, impacting angiogenesis.
- TSP2 plays a significant role in modulating NF-κB activity and inhibiting angiogenesis.
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