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Mar Drugs
2019 Jun 21;176:. doi: 10.3390/md17060368.
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Therapeutic Cell Protective Role of Histochrome under Oxidative Stress in Human Cardiac Progenitor Cells.
Park JH
,
Lee NK
,
Lim HJ
,
Mazumder S
,
Kumar Rethineswaran V
,
Kim YJ
,
Jang WB
,
Ji ST
,
Kang S
,
Kim DY
,
Van LTH
,
Giang LTT
,
Kim DH
,
Ha JS
,
Yun J
,
Kim H
,
Han J
,
Mishchenko NP
,
Fedoreyev SA
,
Vasileva EA
,
Kwon SM
,
Baek SH
.
???displayArticle.abstract???
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.
NRF - 2018R1A2B6006380 National Research Foundation of Korea, NRF - 2015M3A9B4066493 National Research Foundation of Korea, HI18C2459 Korean Health Technology R&D Project, Ministry of Health and Welfare, HI18C2458 Korean Health Technology R&D Project, Ministry of Health and Welfare, HI17C1662 Korean Health Technology R&D Project, Ministry of Health and Welfare, NRF - 2015R1A5A2009656 National Research Foundation of Korea, RFMEFI61317X0076 Ministry of Science and Higher Education of the Russian Federation
Figure 6. Schematic representation of cytoprotective effects of histochrome against H2O2-induced cell death via reduction of DNA damage and activation of survival signaling.
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