Apamin Inhibits THP-1-Derived Macrophage Apoptosis Via
Mitochondria-Related Apoptotic Pathway
Exp Mol Pathol, 2012 Apr 17
The development of atherosclerotic lesions is mainly due to
macrophage death. The oxidative stresses of monocytes/macrophages play a vital
role in the initiation and amplification of atherosclerosis.
Apamin, a component of bee venom, exerts an anti-inflammatory
effect, and selectively inhibits the Ca(2+)-activated K(+) channels. The
mechanisms involved in the inhibition of macrophage apoptosis have been fully
elucidated.
We induced oxidized low-density lipoprotein (oxLDL) in
THP-1-derived macrophage and studied the effect of apamin on intercellular
lipid levels, mitochondria-related apoptotic pathway and numbers of apoptotic
cells. Oil-red O staining indicates that the inhibition of apamin in the
condition significantly prevents intracellular lipid deposition.
Treatment with apamin significantly decreased the apoptotic
macrophages by decreasing the expression of pro-apoptotic genes Bax, caspase-3
and PARP protein levels, as well as through increasing expression of
anti-apoptotic genes Bcl-2 and Bcl-xL protein levels in the absence and
presence of oxLDL. In vivo, with apamin treatment reduced apoptotic cells death
by TUNEL staining.
These results indicate that apamin plays an important role
in monocyte/macrophage apoptotic processing, which may provide a potential drug
for preventing atherosclerosis.