RBM3 expression is upregulated by NF-κB p65 activity, protecting cells from apoptosis, during mild hypothermia

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• RNA-binding protein 3 (RBM3) is a cold shock protein crucial for cell survival under hypothermia.
• The precise mechanisms regulating RBM3 expression and its role in apoptosis during mild hypothermia remain largely unknown.

Purpose of the Study:

• To elucidate the molecular mechanism by which mild hypothermia regulates RBM3 expression and suppresses apoptosis.
• To investigate the role of the transcription factor NF-κB p65 in this process.

Main Methods:

• Investigated the phosphorylation and transcriptional activity of NF-κB p65 under hypothermic conditions.
• Utilized caffeic acid phenethyl ester (CAPE) to inhibit NF-κB p65 translocation.
• Employed gene silencing and overexpression techniques for RBM3 and NF-κB p65.
• Assessed RBM3 mRNA and protein levels, and apoptosis incidence.

Main Results:

• Hypothermia induces phosphorylation of NF-κB p65 at Ser276, leading to RBM3 gene transcription and increased RBM3 protein levels.
• RBM3 upregulation by NF-κB p65 effectively suppresses apoptosis under hypothermic conditions.
• Inhibition of NF-κB p65 by CAPE decreased RBM3 expression and increased apoptosis, even under hypothermia.
• RBM3 overexpression protected against CAPE-induced apoptosis, while RBM3 deficiency enhanced apoptosis.

Conclusions:

• NF-κB p65 is a key mediator linking mild hypothermia to RBM3 expression, thereby preventing apoptosis.
• RBM3 plays a critical role in mediating the anti-apoptotic effects of mild hypothermia.
• CAPE's ability to inhibit RBM3 expression suggests potential therapeutic applications in cancer treatment.