Apurinic/apyrimidinic endodeoxyribonuclease 1
(APE1) is the major enzyme involved in the base excision
repair pathway working on DNA damages mainly
caused by oxidative stress. Namely, APE1 hydrolyses
the phosphodiester bond at the abasic sites generated
by DNA glycosylases, creating the substrate for DNA
polymerase β and DNA ligase IIIa which terminate the
reparative process [1]. APE1 also seems to play a role in
cell senescence maintaining telomere stability and size
in interaction with specifi c telomere-protective proteins
[2]. Here, aortic valve interstitial cells (AVICs) isolated
from healthy bovine valve leafl ets were cultured under
normal conditions for up to 90 days to achieve spontaneous
cell senescence. Time-dependent increase in
β-galactosidase activity, a marker of cell senescence, was
paralleled by a remarkable decrease of APE1-expressing
AVICs starting from day 60, as immunocytochemically
revealed. Quantitative Western blot analyses also showed
a drop of APE1 protein content at day 60, whereas RTPCR
analyses revealed a mild increase of the enzyme
mRNA over time. Ultrastructurally, AVICs appeared
well preserved up to 30-day-long culturing. Conversely,
starting from day 60, cells showed non-lysosomal
autophagocytosis features mainly consisting of a hypertrophic
rough endoplasmic reticulum engulfi ng suff ering
mitochondria [3]. Cytoplasm vacuolization due to
large organelle degeneration was also clearly appreciable.
In conclusion, decreasing APE1 expression over time
is supposed to contribute to AVIC decay in a model of
spontaneous cell senescence.
