MicroRNAs Modulate Oxidative Stress in Hypertension through PARP-1 Regulation.

Abstract

Oxidative stress is thought to contribute to aging and age-related diseases, such as cardiovascular and neurodegenerative diseases, and is a risk factor for systemic arterial hypertension. Previously, we reported differential mRNA and microRNA (miRNA) expression between African American (AA) and white women with hypertension. Here, we found that the poly-(ADP-ribose) polymerase 1 (PARP-1), a DNA damage sensor protein involved in DNA repair and other cellular processes, is upregulated in AA women with hypertension. To explore this mechanism, we identified two miRNAs, miR-103a-2-5p and miR-585-5p, that are differentially expressed with hypertension and were predicted to target PARP1. Through overexpression of each miRNA-downregulated PARP-1 mRNA and protein levels and using heterologous luciferase reporter assays, we demonstrate that miR-103a-2-5p and miR-585-5p regulate PARP1 through binding within the coding region. Given the important role of PARP-1 in DNA repair, we assessed whether overexpression of miR-103a-2-5p or miR-585-5p affected DNA damage and cell survival. Overexpression of these miRNAs enhanced DNA damage and decreased both cell survival and colony formation. These findings highlight the role for PARP-1 in regulating oxidative DNA damage in hypertension and identify important new miRNA regulators of PARP-1 expression. These insights may provide additional avenues to understand hypertension health disparities.

• Authors: Douglas F Dluzen, Yoonseo Kim, Paul Bastian, Yongqing Zhang, Elin Lehrmann, Kevin G Becker, Nicole Noren Hooten, Michele K Evans
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2017 Pg. 3984280 ( 2017) ISSN: 1942-0994 [Electronic] United States
• PMID: 28660007 (Publication Type: Journal Article)

Chemical References

• MicroRNAs
• PARP1 protein, human
• Poly (ADP-Ribose) Polymerase-1

Topics

• Female
• Humans
• Hypertension (genetics, pathology)
• MicroRNAs (metabolism)
• Oxidative Stress
• Poly (ADP-Ribose) Polymerase-1 (metabolism)
• Transfection