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SiO₂ nanoparticle-induced impairment of mitochondrial energy metabolism in hepatocytes directly and through a Kupffer cell-mediated pathway in vitro.

Xue Y, Chen Q, Ding T, Sun J - Int J Nanomedicine (2014)

Bottom Line: First, a buffalo rat liver (BRL) cell line was directly exposed to SiO2 nanoparticles, which induced cytotoxicity and mitochondrial damage accompanied by decreases in mitochondrial dehydrogenase activity, mitochondrial membrane potential, enzymatic expression in the Krebs cycle, and activity of the mitochondrial respiratory chain complexes I, III and IV.The supernatants from Kupffer cells treated with SiO2 nanoparticles were transferred to stimulate BRL cells.We observed that SiO2 nanoparticles had the ability to activate Kupffer cells, leading to release of tumor necrosis factor-α, nitric oxide, and reactive oxygen species from these cells and subsequently to inhibition of mitochondrial respiratory chain complex I activity in BRL cells.

View Article: PubMed Central - PubMed

Affiliation: Shanghai Biomaterials Research and Testing Center, Shanghai Key Laboratory of Stomatology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.

ABSTRACT
The liver has been shown to be a primary target organ for SiO2 nanoparticles in vivo, and may be highly susceptible to damage by these nanoparticles. However, until now, research focusing on the potential toxic effects of SiO2 nanoparticles on mitochondria-associated energy metabolism in hepatocytes has been lacking. In this work, SiO2 nanoparticles 20 nm in diameter were evaluated for their ability to induce dysfunction of mitochondrial energy metabolism. First, a buffalo rat liver (BRL) cell line was directly exposed to SiO2 nanoparticles, which induced cytotoxicity and mitochondrial damage accompanied by decreases in mitochondrial dehydrogenase activity, mitochondrial membrane potential, enzymatic expression in the Krebs cycle, and activity of the mitochondrial respiratory chain complexes I, III and IV. Second, the role of rat-derived Kupffer cells was evaluated. The supernatants from Kupffer cells treated with SiO2 nanoparticles were transferred to stimulate BRL cells. We observed that SiO2 nanoparticles had the ability to activate Kupffer cells, leading to release of tumor necrosis factor-α, nitric oxide, and reactive oxygen species from these cells and subsequently to inhibition of mitochondrial respiratory chain complex I activity in BRL cells.

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Effects of SiO2 particles on the expression of Krebs cycle enzymes (IDH and CS) in BRL cells.Notes: (A) BRL cells were exposed to different concentrations of SiO2 particles for 24 hours. Aliquots of mitochondrial protein were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis and analyzed by Western blotting. COX IV was used as an internal control to monitor for equal loading. Densitometry showing data for (B) IDH and (C) CS. The results are the mean ± standard deviation of three independent experiments. *P<0.05 versus the control.Abbreviations: CS, citrate synthase; IDH, isocitrate dehydrogenase; BRL, buffalo rat liver; COX, cytochrome C oxidase.
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f5-ijn-9-2891: Effects of SiO2 particles on the expression of Krebs cycle enzymes (IDH and CS) in BRL cells.Notes: (A) BRL cells were exposed to different concentrations of SiO2 particles for 24 hours. Aliquots of mitochondrial protein were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis and analyzed by Western blotting. COX IV was used as an internal control to monitor for equal loading. Densitometry showing data for (B) IDH and (C) CS. The results are the mean ± standard deviation of three independent experiments. *P<0.05 versus the control.Abbreviations: CS, citrate synthase; IDH, isocitrate dehydrogenase; BRL, buffalo rat liver; COX, cytochrome C oxidase.

Mentions: Isocitrate dehydrogenase and citrate synthase are enzymes that participate in the Krebs cycle, and were assayed in this study by Western blot. As shown in Figure 5, compared with the negative control, SiO2 nanoparticles inhibited expression of both isocitrate dehydrogenase and citrate synthase at a concentration of 1.0 mg/mL, whereas micrometer SiO2 particles did not. This finding suggests that SiO2 nanoparticles have the potential to disturb the Krebs cycle in BRL cells.


SiO₂ nanoparticle-induced impairment of mitochondrial energy metabolism in hepatocytes directly and through a Kupffer cell-mediated pathway in vitro.

Xue Y, Chen Q, Ding T, Sun J - Int J Nanomedicine (2014)

Effects of SiO2 particles on the expression of Krebs cycle enzymes (IDH and CS) in BRL cells.Notes: (A) BRL cells were exposed to different concentrations of SiO2 particles for 24 hours. Aliquots of mitochondrial protein were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis and analyzed by Western blotting. COX IV was used as an internal control to monitor for equal loading. Densitometry showing data for (B) IDH and (C) CS. The results are the mean ± standard deviation of three independent experiments. *P<0.05 versus the control.Abbreviations: CS, citrate synthase; IDH, isocitrate dehydrogenase; BRL, buffalo rat liver; COX, cytochrome C oxidase.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061170&req=5

f5-ijn-9-2891: Effects of SiO2 particles on the expression of Krebs cycle enzymes (IDH and CS) in BRL cells.Notes: (A) BRL cells were exposed to different concentrations of SiO2 particles for 24 hours. Aliquots of mitochondrial protein were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis and analyzed by Western blotting. COX IV was used as an internal control to monitor for equal loading. Densitometry showing data for (B) IDH and (C) CS. The results are the mean ± standard deviation of three independent experiments. *P<0.05 versus the control.Abbreviations: CS, citrate synthase; IDH, isocitrate dehydrogenase; BRL, buffalo rat liver; COX, cytochrome C oxidase.
Mentions: Isocitrate dehydrogenase and citrate synthase are enzymes that participate in the Krebs cycle, and were assayed in this study by Western blot. As shown in Figure 5, compared with the negative control, SiO2 nanoparticles inhibited expression of both isocitrate dehydrogenase and citrate synthase at a concentration of 1.0 mg/mL, whereas micrometer SiO2 particles did not. This finding suggests that SiO2 nanoparticles have the potential to disturb the Krebs cycle in BRL cells.

Bottom Line: First, a buffalo rat liver (BRL) cell line was directly exposed to SiO2 nanoparticles, which induced cytotoxicity and mitochondrial damage accompanied by decreases in mitochondrial dehydrogenase activity, mitochondrial membrane potential, enzymatic expression in the Krebs cycle, and activity of the mitochondrial respiratory chain complexes I, III and IV.The supernatants from Kupffer cells treated with SiO2 nanoparticles were transferred to stimulate BRL cells.We observed that SiO2 nanoparticles had the ability to activate Kupffer cells, leading to release of tumor necrosis factor-α, nitric oxide, and reactive oxygen species from these cells and subsequently to inhibition of mitochondrial respiratory chain complex I activity in BRL cells.

View Article: PubMed Central - PubMed

Affiliation: Shanghai Biomaterials Research and Testing Center, Shanghai Key Laboratory of Stomatology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.

ABSTRACT
The liver has been shown to be a primary target organ for SiO2 nanoparticles in vivo, and may be highly susceptible to damage by these nanoparticles. However, until now, research focusing on the potential toxic effects of SiO2 nanoparticles on mitochondria-associated energy metabolism in hepatocytes has been lacking. In this work, SiO2 nanoparticles 20 nm in diameter were evaluated for their ability to induce dysfunction of mitochondrial energy metabolism. First, a buffalo rat liver (BRL) cell line was directly exposed to SiO2 nanoparticles, which induced cytotoxicity and mitochondrial damage accompanied by decreases in mitochondrial dehydrogenase activity, mitochondrial membrane potential, enzymatic expression in the Krebs cycle, and activity of the mitochondrial respiratory chain complexes I, III and IV. Second, the role of rat-derived Kupffer cells was evaluated. The supernatants from Kupffer cells treated with SiO2 nanoparticles were transferred to stimulate BRL cells. We observed that SiO2 nanoparticles had the ability to activate Kupffer cells, leading to release of tumor necrosis factor-α, nitric oxide, and reactive oxygen species from these cells and subsequently to inhibition of mitochondrial respiratory chain complex I activity in BRL cells.

Show MeSH
Related in: MedlinePlus