title: Pretreatment with Lycopene Attenuates Oxidative Stress-Induced Apoptosis in Human Mesenchymal Stem Cells.
abstract: Human mesenchymal stem cells (MSCs) have been used in cell-based therapy to promote revascularization after peripheral or myocardial ischemia. High levels of reactive oxygen species (ROS) are involved in the senescence and apoptosis of MSCs, causing defective neovascularization. Here, we examined the effect of the natural antioxidant lycopene on oxidative stress-induced apoptosis in MSCs. Although H2O2 (200 μM) increased intracellular ROS levels in human MSCs, lycopene (10 μM) pretreatment suppressed H2O2-induced ROS generation and increased survival. H2O2-induced ROS increased the levels of phosphorylated p38 mitogen activated protein kinase (MAPK), Jun-N-terminal kinase (JNK), ataxia telangiectasia mutated (ATM), and p53, which were inhibited by lycopene pretreatment. Furthermore, lycopene pretreatment decreased the expression of cleaved poly (ADP ribose) polymerase-1 (PARP-1) and caspase-3 and increased the expression of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax), which were induced by H2O2 treatment. Moreover, lycopene significantly increased manganese superoxide dismutase (MnSOD) expression and decreased cellular ROS levels via the PI3K-Akt pathway. Our findings show that lycopene pretreatment prevents ischemic injury by suppressing apoptosis-associated signal pathway and enhancing anti-oxidant protein, suggesting that lycopene could be developed as a beneficial broad-spectrum agent for the successful MSC transplantation in ischemic diseases.
authors.affiliation: Laboratory for Vascular Medicine & Stem Cell Biology, Medical Research Institute, Department of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea.
authors.forename: Ji Yong
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Animal Science and Technology, Sunchon National University, Suncheon 57922, Republic of Korea.
authors.forename: Jai-Sung
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Medical Science Research Institute, Soonchunhyang University Seoul Hospital, Seoul 04401, Republic of Korea.
authors.forename: Yong-Seok
authors.initials: YS
authors.lastname: Han
authors.affiliation: Laboratory for Vascular Medicine & Stem Cell Biology, Medical Research Institute, Department of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea.
authors.forename: Jun Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Animal Science and Technology, Sunchon National University, Suncheon 57922, Republic of Korea.
authors.forename: Inhyu
authors.initials: I
authors.lastname: Bae
authors.affiliation: Medical Science Research Institute, Soonchunhyang University Seoul Hospital, Seoul 04401, Republic of Korea.
authors.forename: Yeo Min
authors.initials: YM
authors.lastname: Yoon
authors.affiliation: Laboratory for Vascular Medicine & Stem Cell Biology, Medical Research Institute, Department of Physiology, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea.
authors.forename: Sang Mo
authors.initials: SM
authors.lastname: Kwon
authors.affiliation: Medical Science Research Institute, Soonchunhyang University Seoul Hospital, Seoul 04401, Republic of Korea ; Departments of Biochemistry, Soonchunhyang University College of Medicine, Cheonan 31151, Republic of Korea.
authors.forename: Sang Hun
authors.initials: SH
authors.lastname: Lee
keywords: Anti-oxidant reagent; Apoptosis; Lycopene; MSC; Oxidative stress