Dexamethasone-conjugated polyethylenimine as an efficient gene carrier with an anti-apoptotic effect to cardiomyocytes

Hyunjung Kim, Hyun Ah Kim, Yun Mi Bae, Joon Sig Choi, Minhyung Lee

Research output: Contribution to journalArticle

38 Citations (Scopus)

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 antiapoptotic 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.

Original languageEnglish
Pages (from-to)515-522
Number of pages8
JournalJournal of Gene Medicine
Volume11
Issue number5
DOIs
StatePublished - 2009 Jun 1

Fingerprint

Polyethyleneimine
Cardiac Myocytes
Dexamethasone
Heme Oxygenase-1
Transfection
Caspase 3
Genes
Cell Survival
Apoptosis
Genetic Therapy
DNA
Luciferases
Glucocorticoids
Anti-Inflammatory Agents
Molecular Weight
Weights and Measures

Keywords

  • Dexamethasone
  • Gene carrier
  • Heme oxygenase-1
  • Hydrogen peroxide
  • Polyethylenimine

Cite this

Kim, Hyunjung ; Kim, Hyun Ah ; Bae, Yun Mi ; Choi, Joon Sig ; Lee, Minhyung. / Dexamethasone-conjugated polyethylenimine as an efficient gene carrier with an anti-apoptotic effect to cardiomyocytes. In: Journal of Gene Medicine. 2009 ; Vol. 11, No. 5. pp. 515-522.
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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 antiapoptotic 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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Dexamethasone-conjugated polyethylenimine as an efficient gene carrier with an anti-apoptotic effect to cardiomyocytes. / Kim, Hyunjung; Kim, Hyun Ah; Bae, Yun Mi; Choi, Joon Sig; Lee, Minhyung.

In: Journal of Gene Medicine, Vol. 11, No. 5, 01.06.2009, p. 515-522.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Dexamethasone-conjugated polyethylenimine as an efficient gene carrier with an anti-apoptotic effect to cardiomyocytes

AU - Kim, Hyunjung

AU - Kim, Hyun Ah

AU - Bae, Yun Mi

AU - Choi, Joon Sig

AU - Lee, Minhyung

PY - 2009/6/1

Y1 - 2009/6/1

N2 - 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 antiapoptotic 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.

AB - 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 antiapoptotic 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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KW - Gene carrier

KW - Heme oxygenase-1

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