Therapeutic Cell Protective Role of Histochrome under Oxidative Stress in Human Cardiac Progenitor Cells

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.

1,4-Naphthoquinones: Some Biological Properties and Application

“…Moreover, echinochrome was found to be a potential drug for enhancing cardiomyocyte differentiation in embryonic stem cells through direct binding to protein kinase C iota type (PKC-iota) and inhibition of its activity. 37,38) The protective effect of histochrome (echinochrome) pretreatment of human cardiac progenitor cells (hCPCs) against hydrogen peroxide (H 2 O 2 )-induced oxidative stress was investigated. It was found that histochrome-treated hCPCs showed significant protective effects against H 2 O 2 -induced cell death.…”

“…10) which contain phenylamino-phenylthio moieties as significant counterparts demonstrated major antibacterial activity against bacterial strains Staphylococcus aureus, Listeria monocytogenes, E. coli, P. aeruginosa, Salmonella bongori and Klebsiella pneumoniae. [57][58][59] Two naphthoquinone derivatives (38) and (39) (Fig. 10) had potential antimycobacterial activity against three Mycobacterium tuberculosis strains and did not exhibit cross-resistance with isoniazid and rifampicin; they could be promising scaffolds for the development of new therapeutic strategies against tuberculosis.…”

Selected Papers from the Third International Symposium on Life Science

“…Histochrome delayed the progression of cellular senescence in hCPCs. It was concluded that the use of histochrome as biosafe agent is promising as potential therapeutic strategy at application of patients-derived hCPCs to treat cardiovascular diseases [10].…”

Cardiac Stem Cell Therapy, Resident Progenitor Cells and the role of Cellular Signalling; a Review

“…There are ongoing debates related to definitions of cell lineage in cardiac stem cells. Originally believed to have no capacity for self-renewal due to mature cardiomyocytes' exit from the cell cycle, the heart is now believed to be residence to several different populations of stem or progenitor cells, with the potential for cardiac repair [48]. These cells are speculated to originate from a single cardiac stem cell type, and the different populations to represent different physiological stages of the parent stem cell [49].…”