| Info. | Vol.6 - No.1 (2012.03.20) |
|---|---|
| Title | Adenovirus-mediated heme oxygenase-1 gene transfer to neonatal porcine islet-like cluster cells: the effects on gene expression and protection from cell stress |
| Authors | Hye-Jung Yeom1,?/sup>, Han Ro1,? Sol Ji Park2,3, Ju Ho Hong1, Bumrae Cho1, Hwajung Kim1, Sung Joo Kim4, Jong-Ik Hwang5, Byeong Chun Lee2,3, Curie Ahn1,6 & Jaeseok Yang1,7 |
| Institutions | 1Transplantation Research Institute, Seoul National University Hospital, Seoul, Korea 2Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Seoul National University, Seoul, Korea 3Research Institute for Veterinary Science, Seoul National University, Seoul, Korea 4Department of Surgery, Sungkyunkwan University, School of Medicine, Seoul, Korea 5Graduate School of Medicine, Korea University, Seoul, Korea 6Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea 7Transplantation Center, Seoul National University Hospital, Seoul, Korea �These authors contributed equally to this work. Correspondence and requests for materials should be addressed to J. Yang ( jcyjs@dreamwiz.com) |
| Abstract | Porcine islet xenotransplantation is a promising strategy for the treatment of diabetes that overcomes donor shortages. However, islet xenografts are susceptible to oxidative stress and apoptosis. Heme oxygenase-1 (HO-1) has been shown to protect cells from oxidative stress, apoptosis and inflammation. Here, we investigated whether introduction of human HO-1 (hHO-1) into neonatal porcine islet-like cell clusters (NPCCs) can induce beneficial transcriptional changes in NPCCs against cellular stress. NPCCs were transduced with either adenovirus-HO-1 (Ad-HO-1) or control adenovirus-GFP (Ad-GFP). After treatment with hydrogen peroxide (H2O2) for 24 hours, nitrite oxide (NO) production assays were performed to detect oxidative stress. Microarray analysis was performed using a pig oligonucleotide 44 K gene chip. We profiled transcriptional changes to apoptosis, oxidant and inflammatory genes, and real-time PCR analysis was also performed to confirm the microarray results. Survival of NPCCs after treatment with H2O2 was significantly higher in the Ad-HO-1 group (p⁄0.001), and NO production also decreased in the Ad-HO-1 group (p⁄0.01). The microarray results showed that the expression of pro-apoptosis genes such as CASP3, CASP7, CASP10, CIDE-B and CIDE-C was significantly decreased in the Ad-HO-1 virus group (CASP10; p⁄0.05, CASP3, CIDE-C; p⁄0.01, CASP7, CIDE-B; p⁄0.001). We also found that the expression of oxidative stresses genes including COX1, COX2, CYB5A, SDHD and NOS2 was decreased, and that the anti-oxidant genes Gpx1 and SOD2 were increased in the Ad-HO-1 group (NOS2; p⁄0.05, COXI, COX2, CYB5A, SDHD, SOD2, GPX1; p⁄0.001). However, inflammatory gene expression was not significantly changed. Realtime PCR analysis confirmed the results of the microarray analysis. These results shed light on the underlying mechanisms of the protective effects of hHO-1 on porcine islets from cellular stresses and suggest that hHO- 1 could be a promising target gene for the production of transgenic pigs that confer improved islet xenograft survival. |
| Keyword | Hemeoxgenase-1, Adenovirus, Neonatal porcine islet-like cell clusters, Xenotransplantation, Apoptosis, Oxidative stress |
| PDF File |
 # 2010년도 발행분 부터는 Springer 의 BioChip Journal 페이지에서 전문을 열람하실 수 있습니다.
# 학회회원 로그인 후 [ Springer BioChip Journal 열람하기 ] 버튼을 클릭하시면 새창으로 열립니다. |
