2,5‐hexanedione induces bone marrow mesenchymal stem cell apoptosis via inhibition of Akt/Bad signal pathway

Abstract

2,5-Hexanedione (HD) is an important bioactive metabolite of n-hexane and mediates the neurotoxicity of parent compound. Studies show that HD induces apoptotic death of neural progenitor cells. However, its underlying mechanism remains unknown. Mesenchymal stem cells (MSCs) are multipotential stem cells with the ability to differentiate into various cell types and have been used as cell model for studying the toxic effects of chemicals on stem cells. In this study, we exposed rat bone marrow MSCs to 0, 10, 20, and 40 mM HD in vitro. Apoptosis and disruption of mitochondrial transmembrane potential were estimated by immunochemistry staining. The expression of Akt, Bad, phosphorylated Akt (p-Akt), and Bad (p-Bad) as well as cytochrome c in mitochondria and cytosol were examined by Western blot. Moreover, caspase 3 activity, viability, and death of cells were measured by spectrophotometry. Our results showed that HD induced cell apoptosis and increased caspase 3 activity. HD down-regulated the expression levels of p-Akt, p-Bad and induced MMP depolarization, followed by cytochrome c release. Moreover, HD led to a concentration-dependent increase in the MSCs death, which was relative to MSCs apoptosis. However, these toxic effects of HD on the MSCs were significantly mitigated in the presence of IGF, which could activate PI3 K/Akt pathway. These results indicated that HD induced mitochondria-mediated apoptosis in the MSCs via inhibiting Akt/Bad signaling pathway and apoptotic death of MSCs via the signaling pathway. These results might provide some clues for studying further the mechanisms of HD-induced stem cell apoptosis and adverse effect on neurogenesis.

Nanomorphological and mechanical reconstruction of mesenchymal stem cells during early apoptosis detected by atomic force microscopy

“…Moreover, the major metabolite 2,5-hexanedione of the organic solvent n-hexane, which is widely used in adhesive preparation, paints, varnishes, oil-based paint, and the food industry, can induce apoptosis of BMSCs via the mitochondria-mediated caspase-3 pathway [Sun et al, 2018;Chen et al, 2015] and nervous lesions [Cui et al, 2007]. Some chemotherapy drugs, such as arsenic trioxide, which significantly inhibited acute leukemia cells, induced mesenchymal stem cell (MSC) apoptosis through the mitochondria-mediated caspase-3 pathway in the patient's body [Cai et al, 2010].…”

“…In the process of apoptosis, the cell elastic modulus and volume significantly decreased, and the cell surface roughness obviously increased; subsequently, the early apoptosis marker PS was detected, eventually the cells died. In combination with the previous molecular mechanism of stem cell apoptosis [Tower, 2015;Liu et al, 2018;Sun et al, 2018;Chen et al, 2015;Cui, 2007], stem cell apoptosis is not only a biological apoptotic signal cascade process, but is also accompanied by the reconstruction of mechanics and nanomorphology. These findings were helpful for further understanding and mastering the apoptosis of cells from the perspective of mechanics.…”

Induction of Apoptosis and Inhibition of Epithelial Mesenchymal Transition by α‐Mangostin in MG‐63 Cell Lines

“…The relative ratio of green to red fluorescence was significantly increased in experimental groups, suggesting that α -mangostin caused MMP in MG-63 cells to collapse ( Figure 3(b) ). The loss of MMT results in the translocation of cytochrome c from mitochondria into cytosol [ 25 ]. As shown in Figure 3(c) , treatment with α -mangostin 25 μ M significantly increased the release of cytochrome c into the cytosol.…”

Nanomorphological and mechanical reconstruction of mesenchymal stem cells during early apoptosis detected by atomic force microscopy

“…In the process of apoptosis, the cell elastic modulus and volume significantly decreased, and the cell surface roughness obviously increased; subsequently, the early apoptosis marker PS was detected, eventually the cells died. In combination with the previous molecular mechanism of stem cell apoptosis [Tower, 2015; Liu et al, 2018; Sun et al, 2018; Chen et al, 2015; Cui, 2007], stem cell apoptosis is not only a biological apoptotic signal cascade process, but is also accompanied by the modification of cell mechanics and nanomorphology. This study is helpful for further understanding and mastering the apoptosis of cells from the perspective of mechanics.…”

“…One study found that radiation induced apoptosis of BMSCs through mir-22-exotrophic stress, which affected the repair and regeneration of bone tissue in irradiated sites [Liu et al, 2018]. Moreover, the major metabolite 2,5-hexanedione of the organic solvent n-hexane, which is widely used in adhesive preparation, paints, varnishes, oil-based paint, and the food industry, can induce apoptosis of BMSCs via the mitochondria-mediated caspase-3 pathway [Sun et al, 2018; Chen et al, 2015] and nervous lesions [Cui et al, 2007]. Some chemotherapy drugs, such as arsenic trioxide, which significantly inhibited acute leukemia cells, induced mesenchymal stem cell (MSC) apoptosis through the mitochondria-mediated caspase-3 pathway in the patient’s body [Cai et al, 2010].…”