Immunomodulatory Effects of Symplectoteuthis oualaniensis Protamine and Its PEG Derivative on Macrophages: Involvement of PI3K/Akt Signaling, Redox Regulation, and Cell Cycle Modulation

Antioxidants, Journal Year: 2025, Volume and Issue: 14(4), P. 437 - 437

Published: April 4, 2025

Protamine is a promising marine-derived bioactive compound that highly arginine-rich and has demonstrated unique advantages in medical biological research. This study, for the first time, investigates molecular mechanisms underlying immunomodulatory effects of Salmon Sulfate (SPS), Symplectoteuthis oualaniensis (SOP), its polyethylene glycol (PEG) derivative (SOP-PEG) on RAW264.7 macrophages. The results demonstrate both SOP SOP-PEG significantly enhance proliferation cells by promoting secretion pro-inflammatory cytokines nitric oxide (NO), increasing ROS production, improving antioxidant capacity, comparison to SPS. Elevated levels play crucial role enhancing macrophage immune activity, while enhanced defense help maintain redox homeostasis protect against oxidative stress-induced cellular damage. A Western blot analysis reveals notably regulate expression key proteins associated with PI3K/Akt signaling pathway anti-apoptotic mechanisms. Furthermore, flow cytometry indicates significant increase G2/M-phase cell population treatment groups, which corroborated data showing alterations critical regulatory proteins. Notably, exhibits strongest regulating can be attributed stability prolonged bioactivity resulting from PEGylation SOP. comprehensive study how function through multiple mechanisms, including activation, regulation, cycle modulation. It provides valuable insights theoretical foundation their potential applications immunotherapy regulation.

Language: Английский

Deciphering UBE4B phosphorylation dynamics: a key mechanism in p53 accumulation and cancer cell response to DNA damage

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: April 2, 2025

The p53 tumor suppressor protein plays a crucial role in detecting and eliminating various oncogenic threats by promoting processes such as cell cycle arrest, DNA repair, senescence, apoptosis. UBE4B is essential for negatively regulating during normal conditions following damage. In previous studies, we demonstrated that targets phosphorylated degradation response to However, the regulation of relation damage cancer not well understood. this study, show regulated through phosphorylation dephosphorylation mechanism Phosphorylation reduces its binding affinity p53, leading an accumulation cell. Wip1 UBE4B, which stabilizes activity primarily ATR-mediated signaling, with resulting activation p53. When inhibited, there significant increase phosphorylation, more reduction growth. Therefore, understanding how cells DNA-damaging agents could help develop new therapeutic strategies improve prognosis patients.

Language: Английский