Acidification prevents endothelial cell apoptosis by Axl activation

Area of Science:

• Cell Biology
• Physiology
• Biochemistry

Background:

• Acidification due to hypercarbia (high CO2) is known to protect endothelial cells from apoptosis.
• The precise molecular mechanisms underlying this protective effect remain unclear.

Purpose of the Study:

• To investigate the role of tyrosine kinase receptor Axl and its ligand Gas6 in the antiapoptotic effects of acidification on endothelial cells.
• To elucidate the signaling pathways involved in endothelial cell survival under acidic conditions.

Main Methods:

• Human umbilical vein endothelial cells were cultured under normal (pH 7.4) and acidic (pH 7.0) conditions.
• Gene expression and protein levels of Axl and Gas6 were analyzed using cDNA arrays, RT-PCR, Northern blot, and Western blot.
• Functional studies involved overexpression of Axl cDNA and manipulation of Gas6 signaling.

Main Results:

• Acidification (pH 7.0) significantly upregulated Axl expression and phosphorylation in endothelial cells.
• The Gas6/Axl signaling pathway was identified as a key mediator of the protective effect against serum deprivation-induced apoptosis.
• Overexpression of Axl reduced apoptosis, while blocking Axl or Gas6 signaling partially reversed the protective effect of acidification.

Conclusions:

• The Gas6/Axl signaling pathway plays a critical role in promoting endothelial cell survival during acidification.
• Understanding this mechanism could offer therapeutic targets for conditions involving hypercarbic acidosis and endothelial dysfunction.