Rb1 Protects Endothelial Cells from Hydrogen Peroxide-Induced Cell Senescence by Modulating Redox Status

Ding-Hui Liu, Yan-Ming Chen, Yong Liu, Bao-Shun Hao, Bin Zhou, Lin Wu, Min Wang, Lin Chen, Wei-Kang Wu, Xiao-Xian Qian
2011 Biological and Pharmaceutical Bulletin  
Aging is considered as a high risk factor for cardiovascular diseases, especially for atherosclerosis. 1,2) Vascular aging is believed to be associated with pro-oxidant and pro-inflammatory phenotypic and functional changes, which promote the progression of cardiovascular diseases. 3) At the cellular level, senescence is a state of permanent growth arrest in which cells are alive and metabolically active for months, but are unresponsive to mitogenic stimuli. 4) Free radical-dependent cellular
more » ... mage theory was developed since 1956 and remains the theory basis of aging. 5) Accumulating evidence supports the link between oxidative stress and aging by showing that oxidative stress induces cellular senescence. 6-9) Hydrogen peroxide is widely used to achieve oxidative stress-induced premature senescence within a short time period. Ginsenoside Rb1 is one of 40 bioactive extracts from ginseng which has been used as tonic remedy in traditional Chinese Medicine for two thousand years. 10, 11) Previous studies have demonstrated that increased generation of reactive oxygen species (ROS) in the injured vascular can be reversed by Rb1 treatment which provides a protective effect on the vascular injury. 12) Therefore, we postulate that ginsenoside Rb1 may play a role in protecting vascular cells from senescence through modulating the balance of the antioxidant related enzyme and pro-oxidant related enzyme. To evaluate the protective effects of Rb1, we employed human umbilical vascular endothelial cells (HUVECs) as a model and determined the superoxide dismutase (SOD) and malondialdehyde (MDA) levels in the cells treated by Rb1. SOD, along with other enzymatic and non-enzymatic antioxidants, plays a pivotal role in preventing cellular damage caused by ROS. It exerts its role through reducing the superoxide radical to form hydrogen peroxide and oxygen. There are three forms of SODs which are designated as Cu/Zn-SOD (SOD1), mitochondrial Mn-SOD (SOD2), and extracellular SOD (SOD3). 13) SOD1, the most extensively studied antioxidant enzyme, is constitutively expressed in all mammalian cells and is localized in the cell cytosol and the nucleus. 14) MDA is a major and stable end product formed during the peroxidation of lipids and is regarded as marker of lipid peroxidation in tissues. 15) Here, we reported that Rb1 antagonizes H 2 O 2 -induced HUVECs senescence through upregulating endogenous antioxidants SOD and decreasing vascular lipid peroxidation.
doi:10.1248/bpb.34.1072 pmid:21720015 fatcat:tlp43jqvpnarpgmabh2a4f4dkm