Caveolin-1 regulates oxidative stress-induced senescence in nucleus pulposus cells primarily via the p53/p21 signaling pathway in vitro

Abstract

Previous studies have indicated that cellular senescence is a critical underlying mechanism of intervertebral disc degeneration. However, the precise mechanism by which cellular senescence accelerates disc degeneration has not been fully elucidated. Caveolin-1 has recently emerged as an important regulator of cellular senescence. Therefore, the aim of the present study was to investigate whether caveolin-1 is involved in nucleus pulposus (NP) cellular senescence during oxidative stress. PCR was used to detect caveolin-1 mRNA expression and protein expression was detected by western blotting. Caveolin-1 expression at the mRNA and protein levels was markedly increased following treatment with tert-butyl hydroperoxide, and an increase in premature senescence was observed, as determined by senescence-associated β-galactosidase staining and the decline of cellular proliferative ability. In addition, caveolin-1 gene expression was successfully knocked down by lentivirus-mediated RNA interference, which exerted a protective effect against the cellular senescence induced by oxidative stress. Notably, p53 and p21 protein expression, though not p16 protein expression, decreased with caveolin-1 silencing. The results suggested that caveolin-1 may be involved in NP cellular senescence during oxidative stress in vitro, mainly via the p53/p21 signaling pathway. Thus, caveolin-1 may represent a novel therapeutic target for the prevention of intervertebral disc degeneration.

Positive feedback in Cav‐1‐ROS signalling in PSCs mediates metabolic coupling between PSCs and tumour cells

“…Targeted activation of Cav‐1 also removes active substances produced during oxidative stress. The active substances produced by cellular oxidative stress can in turn regulate the expression, degradation, post‐translational modification and mediated membrane transport of Cav‐1 34 . Multiple antioxidants regulate the Cav‐1–mediated signalling pathway in tumour cells to exert their antitumour effects 33 .…”

Icariin modulates the sirtuin/NF‑κB pathway and exerts anti‑aging effects in human lung fibroblasts

“…Furthermore, cav-1 also plays a potential role in the induction of cell senescence ( 26 , 27 ), as cav-1 has been reported to interact with polymerase I and transcript release factor, and accelerate caveolae information, subsequently promoting the activation of the p53/p21 signaling pathway to regulate cellular senescence ( 28 ). A previous study also demonstrated that cav-1 is highly expressed in premature senescence and inhibition of cav-1 by lentivirus-mediated RNA interference has a marked effect on improving cell senescence induced by oxidative stress ( 29 ). The current study observed the activation of p53/p21 signaling and significant upregulation of cav-1 in the D-gal-induced senescence in IMR-90 cells.…”

Involvement of the Endocrine-Disrupting Chemical Bisphenol A (BPA) in Human Placentation

“…CAV1 is a protein that is found in caveolae, which are 50-100 nM wide invaginations of the cell lipid bilayer. The function of CAV1 in the placenta has not been fully elucidated, but it has been implicated in the transport of lipids, glucose homeostasis control, regulation of cell signalling, and membrane trafficking [65][66][67][68][69][70]. CAV1 is also involved in the palmitoylation of ERα, securing it to caveolae/lipid rafts on the cell membrane [71][72][73][74].…”