Yazihan Nuray, Ataoglu Haluk, Akcil Ethem, Yener Burcu, Salman Bulent, Aydin Cengiz
Molecular Biology Research and Development Unit, Faculty of Medicine, Ankara University, Morfoloji Binasi, Sihhiye, Ankara 06100,Turkey.
World J Gastroenterol. 2008 Jan 7;14(1):76-80. doi: 10.3748/wjg.14.76.
To evaluate role of midkine secretion during Cadmium (Cd) exposure in the human hepatocyte cell line Hep3B cells.
Different dosages of Cd (0.5-1-5-10 microg/mL) were applied to Hep3B cells and their effects to apoptosis, lactate dehydrogenase (LDH) leakage and midkine secretion were evaluated as time dependent manner. Same experiments were repeated with exogenously applied midkine (250-5000 pg/mL) and/or 5 microg/mL Cd.
Cd exposure induced prominent apoptosis and LDH leakage beginning from lower dosages at the 48th h. Cd induced midkine secretion with higher dosages (P < 0.001), (control, Cd 0.5-1-5-10 microg/mL respectively: 1123 +/- 73, 1157 +/- 63, 1242 +/- 90, 1886 +/- 175, 1712 +/- 166 pg/mL). Exogenous 500-5000 pg/mL midkine application during 5 microg/mL Cd toxicity prevented caspase-3 activation (control, Cd toxicity, 250, 500, 1000, 2500, 5000 pg/mL midkine+ Cd toxicity, respectively: 374 +/- 64, 1786 +/- 156, 1545 +/- 179, 1203 +/- 113, 974 +/- 116, 646 +/- 56, 556 +/- 63 cfu) LDH leakage and cell death in Hep3B cells (P < 0.001).
Our results showed that midkine secretion from Hep3B cells during Cd exposure protects liver cells from Cd induced cellular damage. Midkine has anti-apoptotic and cytoprotective role during Cd toxicity. Further studies are needed to explain the mechanism of midkine secretion and cytoprotective role of midkine during Cd exposure. Midkine may be a promising therapeutic agent in different toxic hepatic diseases.
评估人肝癌细胞系Hep3B细胞在镉（Cd）暴露过程中中期因子分泌的作用。
将不同剂量的Cd（0.5 - 1 - 5 - 10微克/毫升）作用于Hep3B细胞，并以时间依赖性方式评估其对细胞凋亡、乳酸脱氢酶（LDH）泄漏和中期因子分泌的影响。用外源性中期因子（250 - 5000皮克/毫升）和/或5微克/毫升Cd重复相同实验。
在第48小时，从较低剂量开始，Cd暴露就诱导了明显的细胞凋亡和LDH泄漏。高剂量的Cd诱导中期因子分泌（P < 0.001），（对照组、Cd 0.5 - 1 - 5 - 10微克/毫升组分别为：1123 ± 73、1157 ± 63、1242 ± 90、1886 ± 175、1712 ± 166皮克/毫升）。在5微克/毫升Cd毒性作用期间，外源性应用500 - 5000皮克/毫升中期因子可防止Hep3B细胞中半胱天冬酶 - 3激活（对照组、Cd毒性组、250、500、1000、2500、5000皮克/毫升中期因子 + Cd毒性组分别为：374 ± 64、1786 ± 156、1545 ± 179、1203 ± 113、974 ± 116、646 ± 56、556 ± 63 cfu）、LDH泄漏和细胞死亡（P < 0.001）。
我们的结果表明，Cd暴露期间Hep3B细胞分泌的中期因子可保护肝细胞免受Cd诱导的细胞损伤。中期因子在Cd毒性作用期间具有抗凋亡和细胞保护作用。需要进一步研究来解释中期因子分泌的机制以及Cd暴露期间中期因子的细胞保护作用。中期因子可能是不同毒性肝病中有前景的治疗药物。
