Enhanced protection of Ins-1 beta cells from apoptosis under hypoxia by delivery of DNA encoding secretion signal peptide-linked exendin-4
- Authors
- Kim, Hyun Ah; Lee, Suyeon; Park, Jeong-Hyun; Lee, Sanghyun; Lee, Byung-Wan; Ihm, Sung Hee; Kim, Tae-il; Kim, Sung Wan; Ko, Kyung Soo; Lee, Minhyung
- Issue Date
- Apr-2009
- Publisher
- TAYLOR & FRANCIS LTD
- Keywords
- apoptosis; cytoprotection; exendin-4; glucagon-like peptide-1; hypoxia; signal peptide
- Citation
- JOURNAL OF DRUG TARGETING, v.17, no.3, pp.242 - 248
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF DRUG TARGETING
- Volume
- 17
- Number
- 3
- Start Page
- 242
- End Page
- 248
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/176996
- DOI
- 10.1080/10611860902718664
- ISSN
- 1061-186X
- Abstract
- In this study, we developed an expression system of exendin-4, a glucagon-like peptide (GLP-1) analog, using a secretion signal peptide (SP) to facilitate exendin-4 secretion. For delivery of the exendin-4 expression system, high-molecular-weight polyethylenimine (25 kDa, PEI25k), low-molecular-weight polyethylenimine (2 kDa, PEI2k), and polyamidoamine (PAMAM) dendrimers were evaluated as gene carriers to Ins-1 beta cells. As a result, PEI25k showed the highest transfection efficiency. For the construction of the exendin-4 expression vector, DNA coding the SP sequence was inserted upstream of the exendin-4 cDNA, resulting in the construction of p beta-SP-Ex-4. Transfection assay showed that the secretion level of exendin-4 increased in the p beta-SP-Ex-4 transfected cells, compared with the p beta-Ex-4 transfected cells. To identify the beta-cell protection effect of p beta-SP-Ex-4 delivery, the Ins-1 beta cells were transfected with p beta-SP-Ex-4 or p beta-Ex-4 and incubated under normoxia or hypoxia. An MTT assay showed that the p beta-SP-Ex-4 transfected cells had higher beta-cell viability than the p beta-Ex-4 transfected cells under hypoxia. In addition, the p beta-SP-Ex-4 transfected cells exhibited lower caspase-3 activity than the p beta-Ex-4 transfected cells. Therefore, PEI25k/p beta-SP-Ex-4 complex may be useful to protect isolated beta cells from apoptosis during transplantation.
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