FK866 Protects Human Dental Pulp Cells against Oxidative Stress-Induced Cellular Senescence

Abstract

FK866 possesses various functional properties, such as anti-angiogenic, anti-cancer, and anti-inflammatory activities. We previously demonstrated that premature senescence of human dental pulp cells (hDPCs) was induced by hydrogen peroxide (H2O2). The present study aimed to investigate whether H2O2-induced premature senescence of hDPCs is affected by treatment with FK866. We found that FK866 markedly inhibited the senescent characteristics of hDPCs after exposure to H2O2, as revealed by an increase in the number of senescence-associated β-galactosidase (SA-β-gal)-positive hDPCs and the upregulation of the p21 and p53 proteins, which acts as molecular indicators of cellular senescence. Moreover, the stimulatory effects of H2O2 on cellular senescence are associated with oxidative stress induction, such as excessive ROS production and NADPH consumption, telomere DNA damage induction, and upregulation of senescence-associated secretory phenotype factors (IL-1β, IL-6, IL-8, COX-2, and TNF-α) as well as NF-κB activation, which were all blocked by FK866. Thus, FK866 might antagonize H2O2-induced premature senescence of hDPCs, acting as a potential therapeutic antioxidant by attenuating oxidative stress-induced pathologies in dental pulp, including inflammation and cellular senescence.

Citicoline Eye Drops Protect Trabecular Meshwork Cells from Oxidative Stress Injury in a 3D In Vitro Glaucoma Model

“…Premature senescence is an acute and irreversible phenomenon induced by various stressors [ 37 , 38 ]. Thus, we analyzed the SA-β-gal activity, which is a well-accepted biochemical marker of cell senescence, in untreated and treated HTMCs.…”

“…Finally, citicoline modulated also the release of senescence-related pro-inflammatory cytokines ( Figure 6 ) [ 37 , 38 ].…”

Nicotinamide phosphoribosyltransferase regulates the cell differentiation and mineralization in cultured odontoblasts

“…These data indicate that NAMPT may positively accelerate the differentiation of MDPC-23 cells without inducing cell proliferation. FK866 is known to exert antioxidant effects on other oxidative stress-related human diseases, such as viral infections, cardiovascular diseases, and oral mucosal diseases [ 24 ]. In contrast, the present results showed that the NAMPT inhibitor FK866 [ 25 ] decreased odontoblast formation in MDPC-23 cells ( Figs.…”

Oxidative Stress-Induced Cellular Senescence in Aging Retina and Age-Related Macular Degeneration

“…The activity of SA β-Gal, the expression of p53, and nuclear γH2AX foci are increased in disc cells by hydrogen peroxide [ 76 ]. In human dental pulp cells, hydrogen peroxide activates SA β-Gal activity, the p53/p21 Cip1 pathway, and the secretion of several inflammatory cytokines; collectively, these responses are termed the senescence-associated secretory phenotype (SASP) [ 77 ].…”