1 research outputs found
High-Level Secretion of Pregnancy Zone Protein Is a Novel Biomarker of DNA Damage-Induced Senescence and Promotes Spontaneous Senescence
Identification of unique and specific biomarkers to better
detect
and quantify senescent cells remains challenging. By a global proteomic
profiling of senescent human skin BJ fibroblasts induced by ionizing
radiation (IR), the cellular level of pregnancy zone protein (PZP),
a presumable pan-protease inhibitor never been linked to cellular
senescence before, was found to be decreased by more than 10-fold,
while the level of PZP in the conditioned medium was increased concomitantly.
This observation was confirmed in a variety of senescent cells induced
by IR or DNA-damaging drugs, indicating that high-level secretion
of PZP is a novel senescence-associated secretory phenotype. RT-PCR
examination verified that the transcription of the PZP gene is enhanced
in various cells at senescence or upregulated following DNA damage
treatment in a p53-independent manner. Moreover, pretreatment with
late pregnancy serum containing a high level of PZP led to inhibition
of doxorubicin-induced senescence in A549 cells, and depletion of
PZP in the pregnancy serum could enhance such inhibition. Finally,
the addition of immuno-precipitated PZP complexes into tissue culture
attenuated the growth of A549 cells and promoted the spontaneous senescence.
Therefore, we revealed that high-level secretion of PZP is a novel
and unique feature associated with DNA damage-induced senescence,
and secreted PZP is a positive regulator of cellular senescence, particularly
during the late stage of gestation