Sirtuin 5 Deficiency Increases Disease Severity in Rats with Adjuvant-induced Arthritis

Ni Zhang, Hui Zhang, Betty Yuen Kwan Law, Ivo Ricardo De Seabra Rodrigues Dias, Cong Ling Qiu, Wu Zeng, Hu Dan Pan, Jin Yun Chen, Yan Fu Bai, Jing Lv, Li Qun Qu, Xi Chen, Qi Huang, Wei Zhang, Li Jun Yang, Lu Yu, Yu Han, Guo Xin Huang, Hui Miao Wang, Xiao Lei Sun, Yun Zhang, Hu Qiang He, Wei Dan Luo, Yao Xiao, Jian Zhou, Ting Xu, Qing Chun Huang, Min Wu, Zhi Sheng Huang, Wei Liu, Vincent Kam Wai Wong & Liang Liu

Highlights

  • SIRT5 expression is significantly lower in RA patients and AIA rats, linking its deficiency to increased disease severity.
  • Overexpression of SIRT5 in AIA rats results in reduced arthritis symptoms and improved joint health, underscoring its anti-inflammatory effects.
  • Treatment with ethyl pyruvate effectively mitigates arthritis in SIRT5-deficient rats, suggesting a new therapeutic avenue based on energy metabolism manipulation.

Summary

Sirtuin 5 (SIRT5) is a protein involved in enzymatic activities as a deacetylase, desuccinylase, and demalonylase [1]. This study investigates the role of SIRT5 in rheumatoid arthritis (RA). It demonstrates that SIRT5 levels are significantly lower in RA patients and adjuvant-induced arthritis (AIA) rats compared to healthy controls. The reduced levels of SIRT5 are associated with increased disease severity, including enhanced inflammatory responses and joint damage. This indicates a potential therapeutic role for SIRT5 modulation.

The paper further explores the protective role of SIRT5 against inflammation, where overexpression of SIRT5 in human monocytes leads to reduced release of pro-inflammatory cytokines. In AIA rats, SIRT5 significantly mitigates arthritis symptoms and prevents bone and joint degradation.

Lastly, the research correlates SIRT5 deficiency with disrupted energy metabolism, highlighting increased protein succinylation in rats with SIRT5 gene knocked out (SIRT5−/−). Treatment with ethyl pyruvate (EP), a derivative of pyruvate, not only reverses arthritis symptoms in SIRT5−/− AIA rats but also reduces pro-inflammatory cytokine levels. These findings suggest a novel therapeutic approach for RA by activating SIRT5 to modulate both inflammation and energy metabolism.

N. Zhang et al., “Sirtuin 5 deficiency increases disease severity in rats with adjuvant-induced arthritis,” Cell Mol Immunol, vol. 17, no. 11, pp. 1190–1192, Nov. 2020, doi: 10.1038/s41423-020-0380-4.

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