AI Article Synopsis
- Sirtuin 5 (SIRT5) is an enzyme located in mitochondria that regulates different processes related to metabolism and stress by modifying lysine residues.
- Research using SIRT5 knockout mice indicates that the absence of SIRT5 does not impair the development or function of immune cells when faced with microbial challenges.
- The findings suggest that inhibiting SIRT5 for cancer treatment is unlikely to increase the risk of infections, indicating a favorable safety profile for SIRT5 inhibitors.
Article Abstract
Sirtuin 5 (SIRT5) is a member of the family of NAD-dependent lysine/histone deacetylases. SIRT5 resides mainly in the mitochondria where it catalyzes deacetylation, demalonylation, desuccinylation, and deglutarylation of lysine to regulate metabolic and oxidative stress response pathways. Pharmacologic inhibitors of SIRT5 are under development for oncologic conditions, but nothing is known about the impact of SIRT5 on antimicrobial innate immune defenses. Using SIRT5 knockout mice, we show that SIRT5 deficiency does not affect immune cell development, cytokine production and proliferation by macrophages and splenocytes exposed to microbial and immunological stimuli. Moreover, preclinical models suggest that SIRT5 deficiency does not worsen endotoxemia, and pneumonia, peritonitis, listeriosis, and staphylococcal infection. Altogether, these data support the safety profile in terms of susceptibility to infections of SIRT5 inhibitors under development.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6255879 | PMC |
| http://dx.doi.org/10.3389/fimmu.2018.02675 | DOI Listing |
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