Investigating the effect of lead acetate on rat bone marrow-derived mesenchymal stem cells toxicity: Role of apoptosis

Abstract

Lead exposure continues to be a significant public health problem. Osteoporosis, inhibition of fracture healing, and cartilage functional impairment have been reported from lead exposure. Mesenchymal stem cells (MSCs) are a bone marrow population of cells with the ability to differentiate into various cell types, particularly osteocytes and chondrocytes. Despite intensive investigation on the effect of lead poisoning on various cell types, there is very little if any report on the effect of lead on MSCs. The aim of this study, therefore, was to investigate the effect of lead acetate on rat bone marrow derived MSCs toxicity and its mechanism by examining the role of pro- and anti-apoptotic proteins in this process. It was revealed that lead acetate could induce cell death in a dose-dependent manner using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium (MTT) assay. Compared to controls, the significant over-expression of pro-apoptotic proteins, including Bax, caspases-9, -3, and p53, with no significant change in anti-apoptotic Bcl(2) protein were obtained in lead-treated cells using western blotting analysis. There was a significant increase in DNA fragmentation in treated MSCs compared to controls using flow-cytometry. Finally, it might be concluded that lead acetate could induce cell toxicity and apoptosis in MSCs, causing instability in mitochondria and in turn activation of the intrinsic pathway including over-expression of Bax, caspase 9 and caspase 3, leading to DNA damage and activation of P53.

2,5-hexanedione induced apoptosis in mesenchymal stem cells from rat bone marrow via mitochondria-dependent caspase-3 pathway

“…MSCs have been used as the model system for studies on effects of many chemicals including nerutoxicants on cell proliferation, survival and differentiation10,11,12 ) . Recently, it was reported that some toxicants such as arsenic and lead can induce apoptosis of MSCs13, 14 ) . Moreover, these studies have been widely concerned.…”

Protective Effect of Ginger (<b><i>Zingiber officinale</i></b> Roscoe) Extract against Oxidative Stress and Mitochondrial Apoptosis Induced by Interleukin-1β in Cultured Chondrocytes

“…During apoptosis progress, proapoptotic proteins such as Bax and Bak are localized in the mitochondrial membrane where they increase membrane permeability. In the cytoplasm, the released cytochrome c conjugates with Apaf-1 and procaspase-9 to form the apoptosome complex that activates capase-9 and further activates caspase-3 to induce apoptosis [Sharifi and Mousavi, 2008;Sharifi et al, 2010Sharifi et al, , 2011.…”

Toxic Effects of Heavy Metals on Bone Tissue

“…Direkt olarak kemikte birikim, kemik hücrelerinde toksik etkiye neden olabilir. Çeşitli klinik ve deneysel çalışmalarda kurşun maruziyetinin kemiğin mineral yoğunluğunu ve gücünü azalttığı, kondrosit ve osteoblast fonksiyonlarını inhibe ettiği ve kemik yapımında azalmaya neden olduğu gösterilmiştir (7)(8)(9)(10). İndirekt etkileri ise kemik mineral metabolizmasında görev alan hormonların sentezinden sorumlu olan endokrin organlar üzerine etki ederek kemik metabolizmasında değişikliğe neden olması ve gastrointestinal sistemden kalsiyum emiliminde azalmaya neden olarak D vitaminin aktifleşmesini önlemesiyle gerçekleşir (11)(12)(13).…”