Verga Falzacappa Cecilia, Panacchia Laura, Bucci Barbara, Stigliano Antonio, Cavallo Maria Gisella, Brunetti Ercole, Toscano Vincenzo, Misiti Silvia
Endocrinology, II Faculty of Medicine, University La Sapienza, Rome, Italy.
J Cell Physiol. 2006 Feb;206(2):309-21. doi: 10.1002/jcp.20460.
3,5,3'-triiodothyronine (T3) is essential for the growth and the regulation of metabolic functions, moreover, the growth-stimulatory effect of T3 has largely been demonstrated and the pathways via which T3 promotes cell growth have been recently investigated. Type 1 diabetes (T1D) is due to the destruction of beta-cells, which occurs even through apoptosis. Aim of our study was to analyze whether T3 could have an antiapoptotic effect on cultured beta-cells undergoing apoptosis. We have demonstrated that T3 promotes cell proliferation in islet beta-cell lines (rRINm5F and hCM) provoking an increment in cell number (up to 55%: rRINm5F and 45%: hCM), cell viability, and BrdU incorporation, and regulating the cell cycle-related molecules (cyc A, D1, E, and p27(kip1)). T3 inhibited the apoptotic process induced by streptozocin, S-Nitroso-N-Acetylpenicylamine (SNAP), and H2O2 via regulation of the pro- and anti-apoptotic factors Bcl-2, Bcl-XL, Bad, Bax, and Caspase 3. The T3 protective effect was PI-3 K-, but not MAPK- or PKA-mediated, involving pAktThr308. Thus, T3 could be considered a survival factor protecting islet beta-cells from apoptosis.
3,5,3'-三碘甲状腺原氨酸（T3）对生长及代谢功能调节至关重要，此外，T3的促生长作用已得到充分证实，且其促进细胞生长的途径最近也得到了研究。1型糖尿病（T1D）是由β细胞破坏所致，这种破坏甚至可通过细胞凋亡发生。我们研究的目的是分析T3对正在经历凋亡的培养β细胞是否具有抗凋亡作用。我们已经证明，T3可促进胰岛β细胞系（rRINm5F和hCM）中的细胞增殖，使细胞数量增加（rRINm5F最多增加55%，hCM最多增加45%）、提高细胞活力并增加BrdU掺入量，同时调节细胞周期相关分子（细胞周期蛋白A、D1、E和p27（kip1））。T3通过调节促凋亡和抗凋亡因子Bcl-2、Bcl-XL、Bad、Bax和半胱天冬酶3，抑制链脲佐菌素、S-亚硝基-N-乙酰青霉胺（SNAP）和过氧化氢诱导的凋亡过程。T3的保护作用是由PI-3 K介导的，而非MAPK或PKA介导，涉及pAktThr308。因此，T3可被视为一种保护胰岛β细胞免于凋亡的存活因子。
