Kruppel-like factor 2 (KLF2) regulates endothelial functions by modulating endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) pathway. Tetrahydrobiopterin (BH4) and S-glutathionylation of eNOS play essential roles in eNOS uncoupling and activation. However, the influence of KLF2 on eNOS uncoupling and the mechanism of eNOS activation still remain unknown. A hypoxia and reoxygenation (H/R) model of human umbilical vein endothelial cells (HUVECs) was utilized in this study. Cell viability and the eNOS uncoupling-related oxidative stress index were measured. The Nrf2 inhibitor ML385 and HO-1 siRNA were used to elucidate the mechanism of activation. The results show that overexpression of KLF2 increased the cell viability, reduced the lactate dehydrogenase leakage rate, downregulated the generation of O2•− and ONOO−, and increased NO levels and eNOS activity. Overexpression of KLF2 also increased the BH4/BH2 ratio and the GSH/GSSG ratio, thus significantly improving eNOS uncoupling in the H/R model. KLF2 has no regulatory effect on the upstream-associated proteins in eNOS activation. However, when combined with the Nrf2 inhibitor or HO-1 siRNA, the regulatory effect of KLF2 on eNOS uncoupling was strongly reduced. These results suggest that KLF2 could improve eNOS uncoupling via Nrf2/HO-1 in H/R-induced endothelial injury.
Chemico-Biological Interactions – Elsevier
Published: May 25, 2019
It’s your single place to instantly
discover and read the research
that matters to you.
Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.
All for just $49/month
Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly
Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.
Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.
Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.
All the latest content is available, no embargo periods.
“Hi guys, I cannot tell you how much I love this resource. Incredible. I really believe you've hit the nail on the head with this site in regards to solving the research-purchase issue.”Daniel C.
“Whoa! It’s like Spotify but for academic articles.”@Phil_Robichaud
“I must say, @deepdyve is a fabulous solution to the independent researcher's problem of #access to #information.”@deepthiw
“My last article couldn't be possible without the platform @deepdyve that makes journal papers cheaper.”@JoseServera