RESULTS: To investigate the mechanism underlying the involvement of the Cav-1/β-catenin complex in the subcellular translocation of β-catenin and its subsequent effects on cerebral I/R injury, we treated ischemic brains with ASON (Cav-1 antisense oligodeoxynucleotides) or FTVT (a competitive peptide antagonist of the Cav-1 and β-catenin interaction). Our study demonstrated that the binding of Cav-1 to β-catenin following I/R injury prevented the nuclear accumulation of β-catenin. Treatment with ASON or FTVT after I/R injury significantly increased the levels of nuclear β-catenin. Furthermore, ASON reduced the phosphorylation of β-catenin at Ser33, Ser37, and Thr41, which contributes to its proteasomal degradation, while FTVT increased phosphorylation at Tyr333, which is associated with its nuclear translocation.
CONCLUSIONS: The above results indicate that the formation of the Cav-1/β-catenin complex anchors β-catenin in the cytoplasm following I/R injury. Additionally, both ASON and FTVT treatments attenuated neuronal death in ischemic brains. Our study suggests that targeting the interaction between Cav-1 and β-catenin serve as a novel therapeutic strategy to protect against neuronal damage during cerebral injury.
结果:为了研究Cav-1/β-catenin复合物参与β-catenin亚细胞易位的机制及其对脑I/R损伤的后续影响,我们用ASON(Cav-1反义寡脱氧核苷酸)或FTVT(Cav-1和β-catenin相互作用的竞争性肽拮抗剂)治疗缺血性脑。我们的研究表明,I/R损伤后Cav-1与β-catenin的结合阻止了β-catenin的核积累。I/R损伤后用ASON或FTVT治疗可显着增加核β-连环蛋白的水平。此外,ASON降低了β-catenin在Ser33,Ser37和Thr41的磷酸化,这有助于其蛋白酶体降解,而FTVT在Tyr333处增加磷酸化,这与其核易位有关。
结论:上述结果表明,在I/R损伤后,Cav-1/β-catenin复合物的形成在细胞质中锚定了β-catenin。此外,ASON和FTVT治疗均减轻了缺血性脑中的神经元死亡。我们的研究表明,靶向Cav-1和β-catenin之间的相互作用可作为一种新型的治疗策略,以防止脑损伤期间的神经元损伤。