Therapeutic Cell Protective Role of Histochrome under Oxidative Stress in Human Cardiac Progenitor Cells
Ji Hye Park,
Na-Kyung Lee,
Hye Ji Lim,
Sinthia Mazumder,
Vinoth Kumar Rethineswaran,
Yeon-Ju Kim,
Woong Bi Jang,
Seung Taek Ji,
Songhwa Kang,
Da Yeon Kim,
Le Thi Hong Van,
Ly Thanh Truong Giang,
Dong Hwan Kim,
Jong Seong Ha,
Jisoo Yun,
Hyungtae Kim,
Jin Han,
Natalia P. Mishchenko,
Sergey A. Fedoreyev,
Elena A. Vasileva,
Sang Mo Kwon,
Sang Hong Baek
Affiliations
Ji Hye Park
Laboratory of Regenerative Medicine and Stem Cell Biology, Department of Physiology, Medical Research Institute, School of Medicine, Pusan National University, Yangsan 50612, Korea
Na-Kyung Lee
Laboratory of Regenerative Medicine and Stem Cell Biology, Department of Physiology, Medical Research Institute, School of Medicine, Pusan National University, Yangsan 50612, Korea
Hye Ji Lim
Laboratory of Regenerative Medicine and Stem Cell Biology, Department of Physiology, Medical Research Institute, School of Medicine, Pusan National University, Yangsan 50612, Korea
Sinthia Mazumder
Laboratory of Regenerative Medicine and Stem Cell Biology, Department of Physiology, Medical Research Institute, School of Medicine, Pusan National University, Yangsan 50612, Korea
Vinoth Kumar Rethineswaran
Laboratory of Regenerative Medicine and Stem Cell Biology, Department of Physiology, Medical Research Institute, School of Medicine, Pusan National University, Yangsan 50612, Korea
Yeon-Ju Kim
Laboratory of Regenerative Medicine and Stem Cell Biology, Department of Physiology, Medical Research Institute, School of Medicine, Pusan National University, Yangsan 50612, Korea
Woong Bi Jang
Laboratory of Regenerative Medicine and Stem Cell Biology, Department of Physiology, Medical Research Institute, School of Medicine, Pusan National University, Yangsan 50612, Korea
Seung Taek Ji
Laboratory of Regenerative Medicine and Stem Cell Biology, Department of Physiology, Medical Research Institute, School of Medicine, Pusan National University, Yangsan 50612, Korea
Songhwa Kang
Laboratory of Regenerative Medicine and Stem Cell Biology, Department of Physiology, Medical Research Institute, School of Medicine, Pusan National University, Yangsan 50612, Korea
Da Yeon Kim
Laboratory of Regenerative Medicine and Stem Cell Biology, Department of Physiology, Medical Research Institute, School of Medicine, Pusan National University, Yangsan 50612, Korea
Le Thi Hong Van
Laboratory of Regenerative Medicine and Stem Cell Biology, Department of Physiology, Medical Research Institute, School of Medicine, Pusan National University, Yangsan 50612, Korea
Ly Thanh Truong Giang
Laboratory of Regenerative Medicine and Stem Cell Biology, Department of Physiology, Medical Research Institute, School of Medicine, Pusan National University, Yangsan 50612, Korea
Dong Hwan Kim
Department of Neurosurgery & Medical Research Institute, Pusan National University Hospital, Busan 49241, Korea
Jong Seong Ha
Laboratory of Regenerative Medicine and Stem Cell Biology, Department of Physiology, Medical Research Institute, School of Medicine, Pusan National University, Yangsan 50612, Korea
Jisoo Yun
Laboratory of Regenerative Medicine and Stem Cell Biology, Department of Physiology, Medical Research Institute, School of Medicine, Pusan National University, Yangsan 50612, Korea
Hyungtae Kim
Department of Thoracic and Cardiovascular Surgery, Pusan National University Yangsan Hospital, Yangsan 50612, Korea
Jin Han
National Research Laboratory for Mitochondrial Signaling, Department of Physiology, Department of Health Sciences and Technology, BK21 Plus Project Team, Cardiovascular and Metabolic Disease Center, Inje University College of Medicine, Busan 47392, Korea
Natalia P. Mishchenko
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Vladivostok 690022, Russia
Sergey A. Fedoreyev
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Vladivostok 690022, Russia
Elena A. Vasileva
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Vladivostok 690022, Russia
Sang Mo Kwon
Laboratory of Regenerative Medicine and Stem Cell Biology, Department of Physiology, Medical Research Institute, School of Medicine, Pusan National University, Yangsan 50612, Korea
Sang Hong Baek
Division of Cardiology, Seoul St. Mary’s Hospital, School of Medicine, the Catholic University of Korea, Seoul 06591, Korea
Cardiac progenitor cells (CPCs) are resident stem cells present in a small portion of ischemic hearts and function in repairing the damaged heart tissue. Intense oxidative stress impairs cell metabolism thereby decreasing cell viability. Protecting CPCs from undergoing cellular apoptosis during oxidative stress is crucial in optimizing CPC-based therapy. Histochrome (sodium salt of echinochrome A—a common sea urchin pigment) is an antioxidant drug that has been clinically used as a pharmacologic agent for ischemia/reperfusion injury in Russia. However, the mechanistic effect of histochrome on CPCs has never been reported. We investigated the protective effect of histochrome pretreatment on human CPCs (hCPCs) against hydrogen peroxide (H2O2)-induced oxidative stress. Annexin V/7-aminoactinomycin D (7-AAD) assay revealed that histochrome-treated CPCs showed significant protective effects against H2O2-induced cell death. The anti-apoptotic proteins B-cell lymphoma 2 (Bcl-2) and Bcl-xL were significantly upregulated, whereas the pro-apoptotic proteins BCL2-associated X (Bax), H2O2-induced cleaved caspase-3, and the DNA damage marker, phosphorylated histone (γH2A.X) foci, were significantly downregulated upon histochrome treatment of hCPCs in vitro. Further, prolonged incubation with histochrome alleviated the replicative cellular senescence of hCPCs. In conclusion, we report the protective effect of histochrome against oxidative stress and present the use of a potent and bio-safe cell priming agent as a potential therapeutic strategy in patient-derived hCPCs to treat heart disease.
