Open Access

Silencing of uncoupling protein 2 by small interfering RNA aggravates mitochondrial dysfunction in cardiomyocytes under septic conditions

  • Authors:
    • Guilang Zheng
    • Juanjuan Lyu
    • Shu Liu
    • Jinda Huang
    • Cui Liu
    • Dan Xiang
    • Meiyan Xie
    • Qiyi Zeng
  • View Affiliations

  • Published online on: April 9, 2015     https://doi.org/10.3892/ijmm.2015.2177
  • Pages: 1525-1536
  • Copyright: © Zheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Uncoupling protein 2 (UCP2) regulates the production of mitochondrial reactive oxygen species (ROS) and cellular energy transduction under physiological or pathological conditions. In this study, we aimed to determine whether mitochondrial UCP2 plays a protective role in cardiomyocytes under septic conditions. In order to mimic the septic condition, rat embryonic cardiomyoblast‑derived H9C2 cells were cultured in the presence of lipopolysaccharide (LPS) plus peptidoglycan G (PepG) and small interfering RNA (siRNA) against UCP2 (siUCP2) was used to suppress UCP2 expression. Reverse transcription quantitative-polymerase chain reaction (RT‑qPCR), western blot analysis, transmission electron microscopy (TEM), confocal microscopy and flow cytometry (FCM) were used to detect the mRNA levels, protein levels, mitochondrial morphology and mitochondrial membrane potential (MMP or ΔΨm) in qualitative and quantitative analyses, respectively. Indicators of cell damage [lactate dehydrogenase (LDH), creatine kinase (CK), interleukin (IL)‑6 and tumor necrosis factor (TNF)‑α in the culture supernatant] and mitochondrial function [ROS, adenosine triphosphate (ATP) and mitochondrial DNA (mtDNA)] were detected. Sepsis enhanced the mRNA and protein expression of UCP2 in the H9C2 cells, damaged the mitochondrial ultrastructure, increased the forward scatter (FSC)/side scatter (SSC) ratio, increased the CK, LDH, TNF‑α and IL‑6 levels, and lead to the dissipation of MMP, as well as the overproduction of ROS; in addition, the induction of sepsis led to a decrease in ATP levels and the deletion of mtDNA. The silencing of UCP2 aggravated H9C2 cell damage and mitochondrial dysfunction. In conclusion, our data demonstrate that mitochondrial morphology and funtion are damaged in cardiomyocytes under septic conditions, while the silencing of UCP2 using siRNA aggravated this process, indicating that UCP2 may play a protective role in cardiomyocytes under septic conditions.
View Figures
View References

Related Articles

Journal Cover

June-2015
Volume 35 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Zheng G, Lyu J, Liu S, Huang J, Liu C, Xiang D, Xie M and Zeng Q: Silencing of uncoupling protein 2 by small interfering RNA aggravates mitochondrial dysfunction in cardiomyocytes under septic conditions. Int J Mol Med 35: 1525-1536, 2015.
APA
Zheng, G., Lyu, J., Liu, S., Huang, J., Liu, C., Xiang, D. ... Zeng, Q. (2015). Silencing of uncoupling protein 2 by small interfering RNA aggravates mitochondrial dysfunction in cardiomyocytes under septic conditions. International Journal of Molecular Medicine, 35, 1525-1536. https://doi.org/10.3892/ijmm.2015.2177
MLA
Zheng, G., Lyu, J., Liu, S., Huang, J., Liu, C., Xiang, D., Xie, M., Zeng, Q."Silencing of uncoupling protein 2 by small interfering RNA aggravates mitochondrial dysfunction in cardiomyocytes under septic conditions". International Journal of Molecular Medicine 35.6 (2015): 1525-1536.
Chicago
Zheng, G., Lyu, J., Liu, S., Huang, J., Liu, C., Xiang, D., Xie, M., Zeng, Q."Silencing of uncoupling protein 2 by small interfering RNA aggravates mitochondrial dysfunction in cardiomyocytes under septic conditions". International Journal of Molecular Medicine 35, no. 6 (2015): 1525-1536. https://doi.org/10.3892/ijmm.2015.2177