SurR9C84A protects and recovers human cardiomyocytes from hypoxia induced apoptosis

Ashok, Ajay, Kanwar, Jagat Rakesh, Krishnan, Uma Maheswari and Kanwar, Rupinder Kaur 2017, SurR9C84A protects and recovers human cardiomyocytes from hypoxia induced apoptosis, Experimental cell research, vol. 350, no. 1, pp. 19-31, doi: 10.1016/j.yexcr.2016.10.021.

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Title SurR9C84A protects and recovers human cardiomyocytes from hypoxia induced apoptosis
Author(s) Ashok, AjayORCID iD for Ashok, Ajay
Kanwar, Jagat RakeshORCID iD for Kanwar, Jagat Rakesh
Krishnan, Uma Maheswari
Kanwar, Rupinder Kaur
Journal name Experimental cell research
Volume number 350
Issue number 1
Start page 19
End page 31
Total pages 13
Publisher Elsevier
Place of publication Amsterdam, The Netherlands
Publication date 2017-01-01
ISSN 1090-2422
Keyword(s) Apoptosis
Science & Technology
Life Sciences & Biomedicine
Cell Biology
Summary Survivin, as an anti-apoptotic protein and a cell cycle regulator, is recently gaining importance for its regenerative potential in salvaging injured hypoxic cells of vital organs such as heart. Different strategies are being employed to upregulate survivin expression in dying hypoxic cardiomyocytes. We investigated the cardioprotective potential of a cell permeable survivin mutant protein SurR9C84A, for the management of hypoxia mediated cardiomyocyte apoptosis, in a novel and clinically relevant model employing primary human cardiomyocytes (HCM). The aim of this research work was to study the efficacy and mechanism of SurR9C84A facilitated cardioprotection and regeneration in hypoxic HCM. To mimic hypoxic microenvironment in vitro, well characterized HCM were treated with 100µm (48h) cobalt chloride to induce hypoxia. Hypoxia induced (HI) HCM were further treated with SurR9C84A (1µg/mL) in order to analyse its cardioprotective efficacy. Confocal microscopy showed rapid internalization of SurR9C84A and scanning electron microscopy revealed the reinstatement of cytoskeleton projections in HI HCM. SurR9C84A treatment increased cell viability, reduced cell death via, apoptosis (Annexin-V assay), and downregulated free cardiac troponin T and MMP-9 expression. SurR9C84A also upregulated the expression of proliferation markers (PCNA and Ki-67) and downregulated mitochondrial depolarization and ROS levels thereby, impeding cell death. Human Apoptosis Array further revealed that SurR9C84A downregulated expression of pro-apoptotic markers and augmented expression of HSPs and HTRA2/Omi. SurR9C84A treatment led to enhanced levels of survivin, VEGF, PI3K and pAkt. SurR9C84A proved non-toxic to normoxic HCM, as validated through unaltered cell proliferation and other marker levels. Its pre-treatment exhibited lesser susceptibility to hypoxia/damage. SurR9C84A holds a promising clinical potential for human cardiomyocyte survival and proliferation following hypoxic injury.
Language eng
DOI 10.1016/j.yexcr.2016.10.021
Field of Research 110201 Cardiology (incl Cardiovascular Diseases)
0601 Biochemistry And Cell Biology
1103 Clinical Sciences
Socio Economic Objective 920103 Cardiovascular System and Diseases
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2016, Elsevier Inc.
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Document type: Journal Article
Collections: Faculty of Health
School of Medicine
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