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CXCR4 attenuates cardiomyocytes mitochondrial dysfunction to resist ischaemia-reperfusion injury.

Cai WF, Kang K, Huang W, Liang JL, Feng YL, Liu GS, Chang DH, Wen ZL, Paul C, Xu M, Millard RW, Wang Y - J. Cell. Mol. Med. (2015)

Bottom Line: The increased CXCR4 expression was observed in cardiomyocytes post CXCR4-adenovirus transduction and this OE significantly reduced the cardiomyocyte contractility under basal conditions.Interestingly, this CXCR4-induced mitochondrial protective effect is associated with the enhanced signal transducer and activator of transcription 3 (expression in mitochondria.Consequently, in the presence of H/R, mitochondrial dysfunction was mitigated and cardiomyocyte death was decreased to 65% in the CXCR4 OE group as compared with the control group.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology & Lab Medicine, College of Medicine, University of Cincinnati, Cincinnati, OH, USA.

No MeSH data available.


Related in: MedlinePlus

Overexpression of CXCR4 reduced the HR-induced the death of cardiomyocyte. (A) Representative flow-cytometric pseudo-colour density plots illustrating the distribution of apoptotic and necrotic cardiomyocytes at the basal or HR condition, after either infections of Control- or CXCR4-adenoviral infection. (B) Quantitative analysis of annexin V and eFluor-780 positive cells, (C) DNA fragmentation and (D) the ratios of ADP to ATP under normal and HR condition, in response to Control- or CXCR4- adenoviral infection. n represents six independent experiments *P < 0.05 versus control under normal condition, #P < 0.05 versus control under H/R condition.
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fig06: Overexpression of CXCR4 reduced the HR-induced the death of cardiomyocyte. (A) Representative flow-cytometric pseudo-colour density plots illustrating the distribution of apoptotic and necrotic cardiomyocytes at the basal or HR condition, after either infections of Control- or CXCR4-adenoviral infection. (B) Quantitative analysis of annexin V and eFluor-780 positive cells, (C) DNA fragmentation and (D) the ratios of ADP to ATP under normal and HR condition, in response to Control- or CXCR4- adenoviral infection. n represents six independent experiments *P < 0.05 versus control under normal condition, #P < 0.05 versus control under H/R condition.

Mentions: Transfected myocytes were subjected to H/R to assess any potential alterations elicited by the CXCR4 OE based on an earlier report that activation of SDF-1α/CXCR4 axis can mediate acute cardioprotection in response to global I/R 10. Results showed 2.3-fold augmentation in Annexin V positive cardiomyocytes, as well as 2.9-fold augmentation in eFluor-780 positive cardiomyocytes, in control Ad.GFP-infected cells following H/R. However, the fold changes of Annexin V (apoptotic) and eFluor-780 (necrotic) cells in the CXCR4 group were significantly lower than control group after H/R (Fig.6A and B). These findings were further supported by results obtained with the DNA fragmentation assay. There was 3.7-fold increase in the extent of DNA fragmentation in the control group, while this increase was suppressed in CXCR4 overexpressing group post H/R injury (Fig.6C). Finally, an increase in the ADP/ATP ratio indicated the H/R-induced energy metabolism disorder was significantly reduced in CXCR4 group (Fig.6D).


CXCR4 attenuates cardiomyocytes mitochondrial dysfunction to resist ischaemia-reperfusion injury.

Cai WF, Kang K, Huang W, Liang JL, Feng YL, Liu GS, Chang DH, Wen ZL, Paul C, Xu M, Millard RW, Wang Y - J. Cell. Mol. Med. (2015)

Overexpression of CXCR4 reduced the HR-induced the death of cardiomyocyte. (A) Representative flow-cytometric pseudo-colour density plots illustrating the distribution of apoptotic and necrotic cardiomyocytes at the basal or HR condition, after either infections of Control- or CXCR4-adenoviral infection. (B) Quantitative analysis of annexin V and eFluor-780 positive cells, (C) DNA fragmentation and (D) the ratios of ADP to ATP under normal and HR condition, in response to Control- or CXCR4- adenoviral infection. n represents six independent experiments *P < 0.05 versus control under normal condition, #P < 0.05 versus control under H/R condition.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4549033&req=5

fig06: Overexpression of CXCR4 reduced the HR-induced the death of cardiomyocyte. (A) Representative flow-cytometric pseudo-colour density plots illustrating the distribution of apoptotic and necrotic cardiomyocytes at the basal or HR condition, after either infections of Control- or CXCR4-adenoviral infection. (B) Quantitative analysis of annexin V and eFluor-780 positive cells, (C) DNA fragmentation and (D) the ratios of ADP to ATP under normal and HR condition, in response to Control- or CXCR4- adenoviral infection. n represents six independent experiments *P < 0.05 versus control under normal condition, #P < 0.05 versus control under H/R condition.
Mentions: Transfected myocytes were subjected to H/R to assess any potential alterations elicited by the CXCR4 OE based on an earlier report that activation of SDF-1α/CXCR4 axis can mediate acute cardioprotection in response to global I/R 10. Results showed 2.3-fold augmentation in Annexin V positive cardiomyocytes, as well as 2.9-fold augmentation in eFluor-780 positive cardiomyocytes, in control Ad.GFP-infected cells following H/R. However, the fold changes of Annexin V (apoptotic) and eFluor-780 (necrotic) cells in the CXCR4 group were significantly lower than control group after H/R (Fig.6A and B). These findings were further supported by results obtained with the DNA fragmentation assay. There was 3.7-fold increase in the extent of DNA fragmentation in the control group, while this increase was suppressed in CXCR4 overexpressing group post H/R injury (Fig.6C). Finally, an increase in the ADP/ATP ratio indicated the H/R-induced energy metabolism disorder was significantly reduced in CXCR4 group (Fig.6D).

Bottom Line: The increased CXCR4 expression was observed in cardiomyocytes post CXCR4-adenovirus transduction and this OE significantly reduced the cardiomyocyte contractility under basal conditions.Interestingly, this CXCR4-induced mitochondrial protective effect is associated with the enhanced signal transducer and activator of transcription 3 (expression in mitochondria.Consequently, in the presence of H/R, mitochondrial dysfunction was mitigated and cardiomyocyte death was decreased to 65% in the CXCR4 OE group as compared with the control group.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology & Lab Medicine, College of Medicine, University of Cincinnati, Cincinnati, OH, USA.

No MeSH data available.


Related in: MedlinePlus