Banijamali Mahsan, Rabbani-Chadegani Azra, Shahhoseini Maryam
Department of Biochemistry, Institute Of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
Department of Biochemistry, Institute Of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
J Trace Elem Med Biol. 2016 Jul;36:7-15. doi: 10.1016/j.jtemb.2016.03.008. Epub 2016 Mar 18.
Lead is a poisonous heavy metal that occurs in all parts of environment and causes serious health problems in humans. The aim of the present study was to investigate the possible protective effect of lithium against lead nitrate induced toxicity in non-adherent bone marrow stem cells. Trypan blue and MTT assays represented that exposure of the cells to different concentrations of lead nitrate decreased viability in a dose dependent manner, whereas, pretreatment of the cells with lithium protected the cells against lead toxicity. Lead reduced the number and differentiation status of bone marrow-derived precursors when cultured in the presence of colony stimulating factor (CSF), while the effect was attenuated by lithium. The cells treated with lead nitrate exhibited cell shrinkage, DNA fragmentation, anion superoxide production, but lithium prevented lead action. Moreover, apoptotic indexes such as PARP cleavage and release of HMGB1 induced by lead, were protected by lithium, suggesting anti-apoptotic effect of lithium. Immunoblot analysis of histone H3K9 acetylation indicated that lithium overcame lead effect on acetylation. In conclusion, lithium efficiently reduces lead toxicity suggesting new insight into lithium action which may contribute to increased cell survival. It also provides a potentially new therapeutic strategy for lithium and a cost-effective approach to minimize destructive effects of lead on bone marrow stem cells.
铅是一种有毒重金属，存在于环境的各个部分，并会给人类带来严重的健康问题。本研究的目的是探究锂对硝酸铅诱导的非贴壁骨髓干细胞毒性的可能保护作用。台盼蓝和MTT检测表明，将细胞暴露于不同浓度的硝酸铅会以剂量依赖的方式降低细胞活力，而用锂对细胞进行预处理可保护细胞免受铅毒性影响。当在集落刺激因子（CSF）存在的情况下进行培养时，铅会减少骨髓来源前体细胞的数量和分化状态，而锂可减弱这种作用。用硝酸铅处理的细胞表现出细胞皱缩、DNA片段化、阴离子超氧化物生成，但锂可阻止铅的作用。此外，铅诱导的PARP裂解和HMGB1释放等凋亡指标受到锂的保护，表明锂具有抗凋亡作用。组蛋白H3K9乙酰化的免疫印迹分析表明，锂克服了铅对乙酰化的影响。总之，锂可有效降低铅毒性，这为锂的作用提供了新的见解，可能有助于提高细胞存活率。它还为锂提供了一种潜在的新治疗策略，以及一种经济有效的方法来最小化铅对骨髓干细胞的破坏作用。
