Abstract
Clinical evidence demonstrates that ubiquinol-10, the reduced active form of coenzyme Q10 (CoQ10H2), improves endothelial function through its antioxidant and probably its anti-inflammatory properties. We previously reported that a biomarker combination including miR-146a, its target protein IL-1 receptor-associated kinase (IRAK-1), and released interleukin (IL)-6, here collectively designated as MIRAKIL, indicates senescence-associated secretory phenotype (SASP) acquisition by primary human umbilical vein endothelial cells (HUVECs). We explore the ability of short- and long-term CoQ10H2 supplementation to affect MIRAKIL in HUVECs, used as a model of vascular aging, during replicative senescence in the absence/ presence of lipopolysaccharide (LPS), a proinflammatory stimulus. Senescent HUVECs had the same ability as young cells to internalize CoQ10 and exhibit an improved oxidative status. LPS-induced NF-κB activation diminished after CoQ10H2 pretreatment in both young and senescent cells. However, short-term CoQ10H 2 supplementation attenuated LPS-induced MIRAKIL changes in young cells; in senescent cells CoQ10H2 supplementation significantly attenuated LPS-induced miR-146a and IRAK-1 modulation but failed to curb IL-6 release. Similar results were obtained with long-term CoQ10H2 incubation. These findings provide new insights into the molecular mechanisms by which CoQ10H2 stems endothelial cell inflammatory responses and delays SASP acquisition. These phenomena may play a role in preventing the endothelial dysfunction associated with major age-related diseases.
| Original language | English |
|---|---|
| Pages (from-to) | 410-420 |
| Number of pages | 11 |
| Journal | Free Radical Biology and Medicine |
| Volume | 63 |
| DOIs | |
| Publication status | Published - 2013 |
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Keywords
- Coenzyme Q10
- Free radicals
- HUVEC
- IL-6
- MiR-146a
- Replicative senescence
- SASP
ASJC Scopus subject areas
- Biochemistry
- Physiology (medical)
Cite this
Anti-inflammatory effect of ubiquinol-10 on young and senescent endothelial cells via miR-146a modulation. / Olivieri, Fabiola; Lazzarini, Raffaella; Babini, Lucia; Prattichizzo, Francesco; Rippo, Maria Rita; Tiano, Luca; Di Nuzzo, Silvia; Graciotti, Laura; Festa, Roberto; Brugè, Francesca; Orlando, Patrick; Silvestri, Sonia; Capri, Miriam; Palma, Linda; Magnani, Mauro; Franceschi, Claudio; Littarru, Gian Paolo; Procopio, Antonio Domenico.
In: Free Radical Biology and Medicine, Vol. 63, 2013, p. 410-420.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Anti-inflammatory effect of ubiquinol-10 on young and senescent endothelial cells via miR-146a modulation
AU - Olivieri, Fabiola
AU - Lazzarini, Raffaella
AU - Babini, Lucia
AU - Prattichizzo, Francesco
AU - Rippo, Maria Rita
AU - Tiano, Luca
AU - Di Nuzzo, Silvia
AU - Graciotti, Laura
AU - Festa, Roberto
AU - Brugè, Francesca
AU - Orlando, Patrick
AU - Silvestri, Sonia
AU - Capri, Miriam
AU - Palma, Linda
AU - Magnani, Mauro
AU - Franceschi, Claudio
AU - Littarru, Gian Paolo
AU - Procopio, Antonio Domenico
PY - 2013
Y1 - 2013
N2 - Clinical evidence demonstrates that ubiquinol-10, the reduced active form of coenzyme Q10 (CoQ10H2), improves endothelial function through its antioxidant and probably its anti-inflammatory properties. We previously reported that a biomarker combination including miR-146a, its target protein IL-1 receptor-associated kinase (IRAK-1), and released interleukin (IL)-6, here collectively designated as MIRAKIL, indicates senescence-associated secretory phenotype (SASP) acquisition by primary human umbilical vein endothelial cells (HUVECs). We explore the ability of short- and long-term CoQ10H2 supplementation to affect MIRAKIL in HUVECs, used as a model of vascular aging, during replicative senescence in the absence/ presence of lipopolysaccharide (LPS), a proinflammatory stimulus. Senescent HUVECs had the same ability as young cells to internalize CoQ10 and exhibit an improved oxidative status. LPS-induced NF-κB activation diminished after CoQ10H2 pretreatment in both young and senescent cells. However, short-term CoQ10H 2 supplementation attenuated LPS-induced MIRAKIL changes in young cells; in senescent cells CoQ10H2 supplementation significantly attenuated LPS-induced miR-146a and IRAK-1 modulation but failed to curb IL-6 release. Similar results were obtained with long-term CoQ10H2 incubation. These findings provide new insights into the molecular mechanisms by which CoQ10H2 stems endothelial cell inflammatory responses and delays SASP acquisition. These phenomena may play a role in preventing the endothelial dysfunction associated with major age-related diseases.
AB - Clinical evidence demonstrates that ubiquinol-10, the reduced active form of coenzyme Q10 (CoQ10H2), improves endothelial function through its antioxidant and probably its anti-inflammatory properties. We previously reported that a biomarker combination including miR-146a, its target protein IL-1 receptor-associated kinase (IRAK-1), and released interleukin (IL)-6, here collectively designated as MIRAKIL, indicates senescence-associated secretory phenotype (SASP) acquisition by primary human umbilical vein endothelial cells (HUVECs). We explore the ability of short- and long-term CoQ10H2 supplementation to affect MIRAKIL in HUVECs, used as a model of vascular aging, during replicative senescence in the absence/ presence of lipopolysaccharide (LPS), a proinflammatory stimulus. Senescent HUVECs had the same ability as young cells to internalize CoQ10 and exhibit an improved oxidative status. LPS-induced NF-κB activation diminished after CoQ10H2 pretreatment in both young and senescent cells. However, short-term CoQ10H 2 supplementation attenuated LPS-induced MIRAKIL changes in young cells; in senescent cells CoQ10H2 supplementation significantly attenuated LPS-induced miR-146a and IRAK-1 modulation but failed to curb IL-6 release. Similar results were obtained with long-term CoQ10H2 incubation. These findings provide new insights into the molecular mechanisms by which CoQ10H2 stems endothelial cell inflammatory responses and delays SASP acquisition. These phenomena may play a role in preventing the endothelial dysfunction associated with major age-related diseases.
KW - Coenzyme Q10
KW - Free radicals
KW - HUVEC
KW - IL-6
KW - MiR-146a
KW - Replicative senescence
KW - SASP
UR - http://www.scopus.com/inward/record.url?scp=84879803778&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84879803778&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2013.05.033
DO - 10.1016/j.freeradbiomed.2013.05.033
M3 - Article
C2 - 23727324
AN - SCOPUS:84879803778
VL - 63
SP - 410
EP - 420
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
SN - 0891-5849
ER -