Dexamethasone-conjugated polyethylenimine as an efficient gene carrier with an anti-apoptotic effect to cardiomyocytes
- Authors
- Kim, Hyunjung; Kim, Hyun Ah; Bae, Yun Mi; Choi, Joon Sig; Lee, Minhyung
- Issue Date
- Jun-2009
- Publisher
- WILEY
- Keywords
- dexamethasone; gene carrier; heme oxygenase-1; hydrogen peroxide; polyethylenimine
- Citation
- JOURNAL OF GENE MEDICINE, v.11, no.6, pp.515 - 522
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF GENE MEDICINE
- Volume
- 11
- Number
- 6
- Start Page
- 515
- End Page
- 522
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/176691
- DOI
- 10.1002/jgm.1320
- ISSN
- 1099-498X
- Abstract
- Background
Dexamethasone is a potent glucocorticoid with anti-inflammatory effects. Dexamethasone can protect ischemic cardiomyocytes from apoptosis. To apply the anti-apoptotic effect of dexamethasone to ischemic disease gene therapy, dexamethasone-conjugated polyethylenimine (PEI-Dexa) was synthesized and evaluated as an anti-apoptotic gene carrier.
Methods
PEI-Dexa was synthesized with low molecular weight polyethylenimine (PEI2K, 2 kDa). The transfection efficiency and cytotoxicity of PEI-Dexa were evaluated by luciferase assay and the MTT assay. To evaluate the anti-apoptotic effect, PEI-Dexa/DNA complex was transfected into cells and the cells were treated with H2O2. Cell viability and apoptosis level were measured by the MTT assay and caspase-3 assay, respectively.
Results
A transfection assay into H9C2 rat cardiomyocytes showed that PEI-Dexa had the highest transfection efficiency at an 8 : 1 weight ratio (PEI-Dexa/DNA). At this ratio, PEI-Dexa had higher transfection efficiency than high molecular polyethylenimine (PEI25K, 25 kDa) and PEI2K. In addition, the cytotoxicity of PEI-Dexa was lower than that of PEI25K. To evaluate the anti-apoptotic effect, PEI-Dexa/pSV-Luc or PEI2K/pSV-Luc was transfected into H9C2 cells and the cells were treated with H2O2. PEI-Dexa was found to reduce caspase-3 activity and increase cell viability compared to PEI2K. Heme oxygenase-1 (HO-1) can protect ischemic cardiomyocytes from apoptosis. Therefore, pSV-HO-1 was cloned and transfected into H9C2 cells using PEI-Dexa. The cells transfected with PEI-Dexa/pSV-HO-1 complex had lower caspase-3 activity and higher viability than the cells transfected with PEI-Dexa/pSV-Luc complex after the H2O2 treatment.
Conclusions
PEI-Dexa is an efficient gene carrier with an anti-apoptotic effect and may be useful for anti-apoptotic gene therapy in combination with pSV-HO-1.
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