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Protective role of 5-azacytidine on myocardial infarction is associated with modulation of macrophage phenotype and inhibition of fibrosis.

Kim YS, Kang WS, Kwon JS, Hong MH, Jeong HY, Jeong HC, Jeong MH, Ahn Y - J. Cell. Mol. Med. (2014)

Bottom Line: Nitric oxide was produced by PGN, which was reduced by 77.87% after 5AZ treatment.Ejection fraction (59.00 ± 8.03% versus 42.52 ± 2.58%), contractility (LV dP/dt-max, 8299.76 ± 411.56 mmHg versus 6610.36 ± 282.37 mmHg) and relaxation indices (LV dP/dt-min, -4661.37 ± 210.73 mmHg versus -4219.50 ± 162.98 mmHg) were improved after 5AZ administration.Cardiac fibrosis in the MI+5AZ was 8.14 ± 1.00%, compared with 14.93 ± 2.98% in the MI group (P < 0.05).

View Article: PubMed Central - PubMed

Affiliation: Heart Research Center, Chonnam National University Hospital, Gwangju, South Korea.

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Related in: MedlinePlus

Effect of 5AZ on nuclear factor kappa B (NF-κB) activation and iNOS promoter activity. (A) RAW264.7 cells were stimulated with PGN in the presence of BAY11-7082, an inhibitor of NF-κB. (B) RAW264.7 cells were stimulated with PGN for the indicated time and IκBα was degraded at 30 min. (C) Cells were treated with PGN for 30 min. and cytosolic IκBα was degraded and p65 was translocated to the nuclear fraction. 5AZ did not change PGN-induced IκBα degradation and p65 nuclear translocation. (D) iNOS promoter activity was measured at various times. Promoter activity was significantly increased at 4 hrs and reached a maximum at 8 hrs. Increased promoter activity was reduced after 5AZ treatment.
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fig03: Effect of 5AZ on nuclear factor kappa B (NF-κB) activation and iNOS promoter activity. (A) RAW264.7 cells were stimulated with PGN in the presence of BAY11-7082, an inhibitor of NF-κB. (B) RAW264.7 cells were stimulated with PGN for the indicated time and IκBα was degraded at 30 min. (C) Cells were treated with PGN for 30 min. and cytosolic IκBα was degraded and p65 was translocated to the nuclear fraction. 5AZ did not change PGN-induced IκBα degradation and p65 nuclear translocation. (D) iNOS promoter activity was measured at various times. Promoter activity was significantly increased at 4 hrs and reached a maximum at 8 hrs. Increased promoter activity was reduced after 5AZ treatment.

Mentions: Because iNOS is a well-known target of NF-κB, the NF-κB response to PGN was examined. In PGN-induced RAW264.7 cells, BAY11-7082, an inhibitor of NF-κB, inhibited iNOS by 37.65%, while 5AZ inhibited iNOS by 93.29% (Fig.3A). To confirm the effect of 5AZ on PGN-activated NF-κB, RAW264.7 cells were stimulated with PGN for 30 min., 4 hrs or 24 hrs. IκBα was degraded at 30 min. of PGN stimulation, and iNOS protein was increased significantly at 24 hrs (Fig.3B). This result suggested that the PGN-induced iNOS expression was mediated by NF-κB activation. To examine whether NF-κB activation events were inhibited by 5AZ, cells were stimulated with PGN with or without 5AZ for 30 min. Cytosolic IκBα degradation and nuclear translocation of p65, a subunit of NF-κB, were induced by PGN and were not influenced by 5AZ (Fig.3C).


Protective role of 5-azacytidine on myocardial infarction is associated with modulation of macrophage phenotype and inhibition of fibrosis.

Kim YS, Kang WS, Kwon JS, Hong MH, Jeong HY, Jeong HC, Jeong MH, Ahn Y - J. Cell. Mol. Med. (2014)

Effect of 5AZ on nuclear factor kappa B (NF-κB) activation and iNOS promoter activity. (A) RAW264.7 cells were stimulated with PGN in the presence of BAY11-7082, an inhibitor of NF-κB. (B) RAW264.7 cells were stimulated with PGN for the indicated time and IκBα was degraded at 30 min. (C) Cells were treated with PGN for 30 min. and cytosolic IκBα was degraded and p65 was translocated to the nuclear fraction. 5AZ did not change PGN-induced IκBα degradation and p65 nuclear translocation. (D) iNOS promoter activity was measured at various times. Promoter activity was significantly increased at 4 hrs and reached a maximum at 8 hrs. Increased promoter activity was reduced after 5AZ treatment.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
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fig03: Effect of 5AZ on nuclear factor kappa B (NF-κB) activation and iNOS promoter activity. (A) RAW264.7 cells were stimulated with PGN in the presence of BAY11-7082, an inhibitor of NF-κB. (B) RAW264.7 cells were stimulated with PGN for the indicated time and IκBα was degraded at 30 min. (C) Cells were treated with PGN for 30 min. and cytosolic IκBα was degraded and p65 was translocated to the nuclear fraction. 5AZ did not change PGN-induced IκBα degradation and p65 nuclear translocation. (D) iNOS promoter activity was measured at various times. Promoter activity was significantly increased at 4 hrs and reached a maximum at 8 hrs. Increased promoter activity was reduced after 5AZ treatment.
Mentions: Because iNOS is a well-known target of NF-κB, the NF-κB response to PGN was examined. In PGN-induced RAW264.7 cells, BAY11-7082, an inhibitor of NF-κB, inhibited iNOS by 37.65%, while 5AZ inhibited iNOS by 93.29% (Fig.3A). To confirm the effect of 5AZ on PGN-activated NF-κB, RAW264.7 cells were stimulated with PGN for 30 min., 4 hrs or 24 hrs. IκBα was degraded at 30 min. of PGN stimulation, and iNOS protein was increased significantly at 24 hrs (Fig.3B). This result suggested that the PGN-induced iNOS expression was mediated by NF-κB activation. To examine whether NF-κB activation events were inhibited by 5AZ, cells were stimulated with PGN with or without 5AZ for 30 min. Cytosolic IκBα degradation and nuclear translocation of p65, a subunit of NF-κB, were induced by PGN and were not influenced by 5AZ (Fig.3C).

Bottom Line: Nitric oxide was produced by PGN, which was reduced by 77.87% after 5AZ treatment.Ejection fraction (59.00 ± 8.03% versus 42.52 ± 2.58%), contractility (LV dP/dt-max, 8299.76 ± 411.56 mmHg versus 6610.36 ± 282.37 mmHg) and relaxation indices (LV dP/dt-min, -4661.37 ± 210.73 mmHg versus -4219.50 ± 162.98 mmHg) were improved after 5AZ administration.Cardiac fibrosis in the MI+5AZ was 8.14 ± 1.00%, compared with 14.93 ± 2.98% in the MI group (P < 0.05).

View Article: PubMed Central - PubMed

Affiliation: Heart Research Center, Chonnam National University Hospital, Gwangju, South Korea.

Show MeSH
Related in: MedlinePlus