PARP1 inhibitor (PJ34) improves the function of aging-induced endothelial progenitor cells by preserving intracellular NAD(+) levels and increasing SIRT1 activity

PARP1抑制剂(PJ34)通过维持细胞内NAD(+)水平和增加SIRT1活性来改善衰老诱导的内皮祖细胞的功能。

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Abstract

BACKGROUND: Nicotinamide adenine dinucleotide (NAD(+)) is a critical molecule involved in various biological functions. Poly (ADP-ribose) polymerase 1 (PARP1) and sirtuin 1 (SIRT1) affect cellular NAD(+) levels and play essential roles in regulating metabolism. However, there has been little research on the effects of PARP1 and SIRT1 crosstalk during senescence. METHODS: We isolated endothelial progenitor cells (EPCs) from human umbilical cord blood and treated them with a PARP1 inhibitor (PJ34). RESULTS: Using a stress-induced premature aging model built by H(2)O(2), transfection with adenoviral vectors, and Western blot analysis, we observed that PJ34 treatment preserved intracellular NAD(+) levels, increased SIRT1 activity, decreased p53 acetylation, and improved the function of stress-induced premature aging EPCs. CONCLUSIONS: Our results suggest that PJ34 improves the function of aging-induced EPCs and may contribute to cellular therapies for atherosclerosis.

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