MT-CO1 expression in nine organs and tissues of different-aged MRL/lpr mice: Investigation of mitochondrial respiratory chain dysfunction at organ level in systemic lupus erythematosus pathogenesis
Xinglan Huang1, Peng Yan2, Xinghua Song3, Suiying Zhang4, Yuqiong Deng1, Caifeng Huang1, Xiaoqing Zhao1, Sheng Liu1, Xiping Cheng1, Dongjiang Liao2
1Department of Dermatology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
2Department of Respiratory Medicine, State Key Laboratory of Respiratory Diseases, Guangzhou, China
3The First Affiliated Hospital of Guangzhou Medical University, Traditional Chinese Medicine, Guangzhou, China
4Department of Dermatology, Dongguan Songshanhu Central Hospital, Dongguan, China
Keywords: Cytochrome C oxidase subunits 1, malondialdehyde, oxidative stress, systemic lupus erythematosus.
Objectives: This study aims to investigate the expression patterns of mitochondrially encoded cytochrome c oxidase 1 (MT-CO1) in different organs and tissues of MRL/lpr mice aged six and 18 weeks.
Materials and methods: Six-week-old female MRL/lpr mice (n=10) were considered young lupus model mice, and 18-week-old MRL/lpr mice (n=10) were considered old lupus model mice. Additionally, six-week-old (n=10) and 39-week-old (n=10) female Balb/c mice were used as the young and old controls, respectively. The messenger ribonucleic acid (mRNA) and protein expression levels of MT-CO1 in nine organs/tissues were detected via quantitative polymerase chain reaction (qPCR) and Western blot. Malondialdehyde (MDA) levels were determined with thiobarbituric acid colorimetry. The correlation coefficient of MT-CO1 mRNA levels and MDA levels in each organ/tissue at different ages was analyzed by Pearson correlation analysis.
Results: The results showed that most non-immune organs/tissues (heart, lung, liver, kidneys, and intestines) showed increased MT-CO1 expression levels in younger MRL/lpr mice (p<0.05) and decreased MT-CO1 expression in older mice (p<0.05). Expression of MT-CO1 in the lymph nodes was low in younger mice but high in older mice. In other immune organs (spleen and thymus), MT-CO1 expression was low in older MRL/lpr mice. Lower mRNA expression and higher MDA levels were observed in the brains of MRL/lpr mice. However, all MRL/lpr mice showed higher MDA levels than Balb/c mice in every organ no matter younger or older MRL/lpr mice.
Conclusion: Our study results suggest that lymphoid mitochondrial hyperfunction at organ level may be an important intrinsic pathogenesis in systemic lupus erythematosus activity, which may affect mitochondrial dysfunction in non-immune organs.
Citation: Huang X, Yan P, Song X, Zhang S, Deng Y, Huang C, et al. MT-CO1 expression in nine organs and tissues of different-aged MRL/lpr mice: Investigation of mitochondrial respiratory chain dysfunction at organ level in systemic lupus erythematosus pathogenesis. Arch Rheumatol 2022;37(4):504-516.
The study protocol was approved by the Laboratory Animal Ethics Committee of Affiliated First Hospital of Guangzhou Medical University (date: 1.7.2020, no: 202021). The animal research followed the standard of the Animal Research: Reporting of in vivo Experiments (ARRIVE) guidelines.
Data Sharing Statement:
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Wrote the manuscript: X.H., P.Y.; Designed experiments: X.S., S.Z.; Performed experiments: Y.D., C.H.; Analyzed experiments: X.Z., S.L.; Modified manuscript: X.C., D.L.
The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.
This work was supported by the National Natural Science Foundation of China (grant no. 81673983 and 82074172) and the Zhongnanshan Medical Foundation of Guangdong Province (ZNSA-2020013).