Metformin prevented high glucose-induced endothelial reactive oxygen species via OGG1 in an AMPKα-Lin-28 dependent pathway

Abstract

Metformin improved vascular function in obese type 2 diabetic patients. 8-oxoguanine glycosylase (OGG1), a main DNA glycosylase, was involved in vascular complications in diverse diseases. However, whether metformin suppressed endothelial ROS via OGG1 pathway was unclear. Human umbilical vein endothelial cells (HUVECs) were exposed to HG (high glucose) or HG with metformin. OGG1 and AMPfα levels were measured after metformin treatment while HG-caused ROS was measured by DHE prober. Diabetic mice were induced by daily intraperitoneal injections of streptozotocin (STZ). Metformin reduced Endothelial ROS caused by HG via upregulating OGG1. Additionally, OGG1 protein expression was dependent on its mRNA stability, which was reversed by genetic inhibition of AMPKα and Lin-28. The role of OGG1 on ROS stimulated by HG was partially dependent on NFKB/NOX4 pathway in HUVECs. These results suggested that metformin contacted HG-induced endothelial ROS via AMPKα/Lin-28/OGG1 pathway.

Mechanism underlying circularRNA_014301‑mediated regulation of neuronal cell inflammation and apoptosis

“…GAPDH (forward, 5'-GCTCTC TGCTCCTCCCTGTTCTA-3'; and reverse, 5'-TGGTAACCA GGCGTCCGATA-3') and U6 (forward, 5'-AAAGCAAAT CATCGGACGACC-3'; and reverse, 5'-GTACAACACATT GTTTCCTCGGA-3') were used as the internal reference genes (37,38). The primer sequences of 18S RNA (forward, 5'-TGTGCCGCTAGAGGTGAAATT-3', and reverse 5'-TGG CAAATGCTTTCGCTTT-3') were based on Tao et al (39). The primer sequences of circRNA_014301 (forward, 5'-GCT GCTCTAGTGGTGACTCATG-3'; and reverse 5'-TTCTCC ATTCATCCAATCAACTTCG-3'), IL-1β (forward, 5'-GAC CTTCCAGGATGAGGACA-3'; and reverse 5'-AGCTCA TATGGGTCCGACAG-3'), IL-6 (forward, 5'-AGTTGCCTT CTTGGGACTGA-3'; and reverse 5'-CAGAATTGCCAT TGCACAAC-3') and TNF-α (forward, 5'-ACGGCATGGATC TCAAAGAC-3'; and reverse 5'-GTGGGTGAGGAGCAC GTAGT-3') were based on Gonzales et al (40).…”

Metformin in cardiovascular diabetology: a focused review of its impact on endothelial function

“…Moreover, as the main DNA glycosylase, 8-oxoguanine glycosylase 1 (OGG1) can resist ROS and is involved in various vascular diseases. The level of OGG1 increases under metformin (0.5 mM) treatment through the AMPK/Lin-28/OGG1 pathway 216 . The anti-oxidative function of metformin (10 μM-1 mM) also relates to inhibition of TRAF3-interacting protein 2 (TRAF3IP2), which is a redox-sensitive cytoplasmic adapter protein functions upstream of IKK/NF-κB and c-Jun N-terminal kinase (JNK)/AP-1 (Activator protein-1) 217 .…”