CR6 interacting factor 1 deficiency induces premature senescence via SIRT3 inhibition in endothelial cells

Kim, Seonhee; Piao, Shuyu; Lee, Ikjun; Nagar, Harsha; Jeon, Byeong Hwa; Shin, Nara; Kim, Dong Ho; Shong, Minho; Kim, Cuk-Seong

doi:10.1016/j.freeradbiomed.2020.02.017

“…Thus, therapies targeting endothelial senescence would have important clinical implications for the treatment of senescence-related diseases including cardiovascular diseases [ 7 , 8 ]. Furthermore, three main routes lead to senescence: telomere-dependent replicative senescence, oncogene-induced senescence, and stress-induced (premature) senescence [ 9 ]. The mechanisms of senescence are very complex, and thus remain poorly understood.…”

Section: Introductionmentioning

confidence: 99%

The Protective Effect of Chlorogenic Acid on Vascular Senescence via the Nrf2/HO-1 Pathway

Hada

¹

,

Uchida

²

,

Otaka

³

et al. 2020

IJMS

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The world faces the serious problem of aging. In this study, we aimed to investigate the effect of chlorogenic acid (CGA) on vascular senescence. C57/BL6 female mice that were 14 ± 3 months old were infused with either Angiotensin II (AngII) or saline subcutaneously for two weeks. These mice were administered CGA of 20 or 40 mg/kg/day, or saline via oral gavage. AngII infusion developed vascular senescence, which was confirmed by senescence associated-β-galactosidase (SA-β-gal) staining. CGA administration attenuated vascular senescence in a dose-dependent manner, in association with the increase of Sirtuin 1 (Sirt1) and endothelial nitric oxide synthase (eNOS), and with the decrease of p-Akt, PAI-1, p53, and p21. In an in vitro study, with or without pre-treatment of CGA, Human Umbilical Vein Endothelial Cells (HUVECs) were stimulated with H2O2 for an hour, then cultured in the absence or presence of 0.5–5.0 μM CGA for the indicated time. Endothelial cell senescence was induced by H2O2, which was attenuated by CGA treatment. Pre-treatment of CGA increased Nrf2 in HUVECs. After H2O2 treatment, translocation of Nrf2 into the nucleus and the subsequent increase of Heme Oxygenase-1 (HO-1) were observed earlier in CGA-treated cells. Furthermore, the HO-1 inhibitor canceled the beneficial effect of CGA on vascular senescence in mice. In conclusion, CGA exerts a beneficial effect on vascular senescence, which is at least partly dependent on the Nuclear factor erythroid 2-factor 2 (Nrf2)/HO-1 pathway.

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“…2). The first global survey of lysine propionylation has been (Yoon & Kim, 2016;Kim et al, 2020). In this study, the expression of Pgc1α and Err in zebrafish intestine and ZF4 cells showed no significant alteration in response to HFSP0.5 diet and OPP treatment ( Supplementary Fig.…”

Section: Discussionmentioning

confidence: 69%

Dietary propionate induces intestinal oxidative stress via inhibition of SIRT3-mediated SOD2 depropionylation

Ding

¹

,

Zhang

²

,

Liu

³

et al. 2020

Preprint

0

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Propionate is a commonly used preservative in various food and feedstuffs and has been regarded as a food additive without safety concerns. However, we observed that dietary propionate supplementation induced intestinal damage in the context of high fat diet (HFD) in zebrafish. The intestinal damage was attributable to oxidative stress owing to impaired antioxidant capacity, which was caused by compromised SOD2 activity in the intestine. Global lysine propionylation analysis of the intestinal samples showed that SOD2 was propionylated at K132, and further biochemical assays demonstrated that K132 propionylation suppressed SOD2 activity. In addition, SIRT3 could directly interact with SOD2 and played an important role in regulating SOD2 activity via modulating depropionylation, and the enhanced SOD2 propionylation in zebrafish fed high fat plus propionate diet was attributable to reduced SIRT3 expression. Finally, we reveal that intestinal oxidative stress resulting from SOD2 propionylation contributed to the compositional change of gut microbiota, which further deteriorated intestinal oxidative stress independent of SIRT3. Collectively, the results in this study reveal a link between protein propionylation and intestine health, and suggest potential risk of a widely used food preservative in HFD context.

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“…In contrast to our results, Kwak et al demonstrate spermidine as a phase 2 enzyme inducer due to NRF2-ARE pathway activation [ 37 ]. In addition, recent studies indicate that NRF2 binds directly to the SIRT3 promoter, which leads to an increase in its expression [ 41 , 42 ]. Although resveratrol increased NRF2 expression in our study, NRF2 further did neither stimulate SIRT3 expression nor IL6 secretion was reduced.…”

Section: Discussionmentioning

confidence: 99%

Epigallocatechin Gallate Effectively Affects Senescence and Anti-SASP via SIRT3 in 3T3-L1 Preadipocytes in Comparison with Other Bioactive Substances

Lilja

¹

,

Oldenburg

²

,

Pointner

³

et al. 2020

Oxidative Medicine and Cellular Longevity

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Aim. We investigated different bioactive compounds including epigallocatechin gallate (EGCG), anthocyanidin, resveratrol, phloretin, spermidine, butyrate, and β-hydroxybutyrate with regard to their effect on SIRT3 via NRF2 and modulation of the proinflammatory senescence-associated secretory phenotype (SASP) in senescence induced 3T3-L1 preadipocytes. Methods. For induction of senescence, 3T3-L1 preadipocytes were incubated with bromodeoxyuridine (BrdU) for 8 days. Cell cycle inhibition was observed, and β-galactosidase activity was measured. After BrdU treatment, cells were treated with different bioactive compounds in various concentrations for 96 h. ELISA was used for determining proinflammatory cytokine IL6 in SASP cells. Results. CDKN1a increased significantly after BrdU incubation compared to untreated control ( p < 0.01 ). All secondary plant ingredients used for treatment, but not anthocyanidin 50 μM, decrease CDKN1a expression ( p < 0.05 ), whereas most endogenous substances did not attenuate CDKN1a. IL6 secretion positively correlated with CDKN1a ( p < 0.01 ), whereas EGCG could diminish both, IL6 and CDKN1a with the strongest effect ( p < 0.01 ). Although NRF2 positively correlated with SIRT3 activation ( p < 0.05 ), only resveratrol ( p < 0.01 ) and anthocyanidin ( p < 0.05 ) could activate NRF2 significantly. Solely anthocyanidin 50 μM ( p < 0.05 ) and 100 μM ( p < 0.01 ) and EGCG 50 μM ( p < 0.01 ) could increase SIRT3 expression. Activation of SIRT3 with EGCG correlated with lowered IL6 secretion significantly ( p < 0.05 ) but not with anthocyanidin. Conclusion. Accumulation of senescent cells in adipose tissue plays an important role in obesity and age-related diseases. SIRT3, located in the mitochondria, can regulate ROS via different pathways. Thus, targeting SIRT3 activating compounds such as EGCG may delay senescence of cells and senescence induced inflammatory processes.

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CR6 interacting factor 1 deficiency induces premature senescence via SIRT3 inhibition in endothelial cells

Cited by 24 publications

References 42 publications

The Protective Effect of Chlorogenic Acid on Vascular Senescence via the Nrf2/HO-1 Pathway

The Protective Effect of Chlorogenic Acid on Vascular Senescence via the Nrf2/HO-1 Pathway

Dietary propionate induces intestinal oxidative stress via inhibition of SIRT3-mediated SOD2 depropionylation

Epigallocatechin Gallate Effectively Affects Senescence and Anti-SASP via SIRT3 in 3T3-L1 Preadipocytes in Comparison with Other Bioactive Substances

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