Effects of cyclosporin A on gene expression profiles of NIT-1 pancreatic β cell line

Abstract

Abstract: Objective To observe the effects of cyclosporin A (CsA) on gene expression profiles of NIT-1 pancreatic β cells cell line using microarray technique. Methods NIT-1 cells were exposed to cyclosporin A treatment (10 μmol/L) for 24 h and the differential gene expressions were assessed using microarray technique. Results After 24h of CsA treatment,38 of the 4096 genes tested were up-regulated,including 13 genes with known functions involving stress response,cell growth and protein synthesis.Meanwhile 46 genes were down-regulated,including 25 genes with known functions involving cell growth and maturation,oxidative phosphorylation and protein synthesis.Changes of gene expression of Zfr,Tpi and Pax6 were confirmed by semi-quantitative reverse transcription polymerase chain reaction. Conclusions CsA treatment for 24 h induces changes in the gene expression profiles of NIT-1 pancreatic β cells.Down-regulation of the genes related to cell growth and maturation,oxidative phosphorylation and protein synthesis may partly explain the mechanisms that CsA inhibits the release of insulin from pancreatic β cells.

CLC Number:

R966

JIA Zhi-min, XU Wei, YU Le, ZHANG Jia-jie, LÜ Lin, LEI Lin-sheng, WU Shu-guang. Effects of cyclosporin A on gene expression profiles of NIT-1 pancreatic β cell line[J]. Journal of Southern Medical University, 2005, 25(07): 853-857.

References

[1] Yamanoto H, Akazawa S, yamaguchi Y, et al. Effects ofcyclosporin A and low dosages of steroid on posttransplantation diabetes in kidney transplant recipients [J]. Diabetes Care, 1991, 14 (10):867-70.
[2] Hahn HJ, Laube F, Lucke S, et al. Toxic effects ofcyclosporine on the endocrine pancreas of Wistar rats [J]. Transplantation, 1986, 41(1): 44-7.
[3] 余乐,雷林生,吴曙光.环孢霉素A抑制NIT-1胰岛β细胞胰岛素释放并下调线粒体氧化磷酸化酶系基因的表达[J].第一军医大学学报,2003,23(8),833-836.Yu L, Lei LS, Wu SG. Cyclosporin A inhibits insulin release and dowm-regulate gene expressions of mitochondrial oxidative phosphorylation enzymes in NIT-1 cells [J]. J First Mil Med Univ/Di Yi Jun Yi Da Xue Xue Bao, 2003, 23(8): 833-6.
[4] Schna M, Schalon D, Davis R W, et al. Quantitative monitoring of gene expression patterns with a complementary DNA microarray[J]. Science, 1995, 270: 567-70.
[5] Li Y, Li YL, Tang R, et al. Discovery and analysis ofhepatocellular carcinoma genes using cDNA microarrays [J]. J Cancer Res Clin Oncol, 2002, 128: 369-79.
[6] Strandell E, Buschard K, Saldeen J, et al. Interleukin-1 beta induces the expression of Hsp70, heme oxygennase and Mn-SOD in FACS-purified rat islet beta-cells, but not in alpha-cells [J].Immunol Lett, 1995, 48(2): 145-8.
[7] Sai X, Kawamura Y, KokameK, et al. Endoplasmic reticulum stress-inducible protein, Herp, enhances presenilin-mediated generation of amyloid beta-protein[J]. J Biol Chem, 2002, 277: 12915-20.
[8] Smith CM, Steitz JA. Classification of gas5 as a multi-smallnucleolar-RNA (snoRNA) host gene and a member of the 5-prime terminal oligopyrimidine gene family reveals common features of snoRNA host genes[J]. Mol Cell Biol, 1998, 18: 6897-909.
[9] Yasuda T, Kajimoto Y, Fujitani Y, et al. PAX6 mutation as a genetic factor common to aniridia and glucose intolerance [J]. Diabetes,2002, 51(1): 224-30.
[10] Hill ME, Asa SL, Drucker DJ, et al. Essential requirement for Pax6in control of enteroendocrine proglucagon gene transcription [J].Mol Endocrinol, 1999, 13(9): 1474-86.
[11] Duchen MR, Smith PA, Ashcroft FM. Substrate-dependent changes in mitochondrial fumction, intracellular free calcium concentration and membrane channels in pancreatic beta-cells [J]. Biochem J,1993, 294(Pt1): 35-42.
[12] Dufer M, Krippeit-Drews P, Lembert N, et al. Diabetogenic effect of cyclosporin A is mediated by interference with mitochondrial function of pancreatic B-cells [J]. Mol Pharmacol, 2001, 60(4):873-9.
[13] Taylor V, Suter U. Epithelial membrane protein-2 and epithelial membrane protein-3: two novel members of the peripheral myelin protein 22 gene family[J]. Gene, 1996,175:115-20.
[14] Hassan Z, Mohan V, Ali L, et al. SPINK1 is a susceptibility gene for fibrocalculous pancreatic diabetes in subjects from the Indian subcontinent [J]. Am J Hum Genet, 2002, 71: 964-8.