Expression of Active Apurinic Apyrimidinic Endodeoxyribonuclease 1 in Human Platelets

The pivotal role of platelets (PLTs) in hemostasis, thrombosis, innate immunity, and tissue repair is sustained by mitochondria, whose dysfunctions can impair ATP generation and redox signaling, thus affecting optimal levels of PLTs' functionality. Maintenance of mtDNA integrity is essential for mitochondria functioning and is primarily exerted by the base excision repair (BER) pathway, never described in PLTs. Here, we provide the first evidence for the expression levels and subcellular localization of apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1), evaluated alongside cytosolic and mitochondrial markers, in resting human PLTs (huPLTs) isolated from a cohort of healthy donors. A variable expression of APE1 was detected independently of age and sex, and it was found to correlate with the specific enzymatic activity on canonical and far less on noncanonical substrates. Preliminary experiments with an APE1 enzymatic inhibitor suggest a possible involvement of APE1 in PLTs aggregation stimulated by epinephrine. Overall, our findings pave the way for understanding a novel unforeseen role of APE1 in PLTs physiology, which specifically deserves future investigation.