Instant Access to the Journals You Need

for just $40 per month.

SUMOylation Attenuates Sensitivity toward Hypoxia- or Desferroxamine-Induced Injury by Modulating Adaptive Responses in Salivary Epithelial Cells

SUMOylation Attenuates Sensitivity toward Hypoxia- or Desferroxamine-Induced Injury by Modulating Adaptive Responses in Salivary Epithelial Cells

Abstract

Hypoxic stress activates various signal transduction pathways including posttranslational modification with the ubiquitin-like SUMO protein (SUMOylation). However, the molecular mechanisms by which SUMOylation regulates hypoxic responses remain unclear. Here, we investigated the ability of rat salivary Pa-4 epithelial cells to resist cell injury elicited by 1% O 2 - or hypoxia-mimetic desferroxamine (DFO)-stimulated SUMOylation processes. By using Pa-4 cells stably transduced with lenti-SUMO-1 and a cell-permeant peptide harboring SUMO-binding motif to interfere with SUMO-dependent protein-protein interactions, we demonstrate that SUMOylation augments cell survival against DFO treatment. This appeared to be partly mediated through attenuation of Protein Kinase C (PKC)- activation and caspase-3 cleavage, hallmarks of pro-apoptotic signaling. Intriguingly, DFO-induced phosphorylation of DNA damage marker ataxia-telangiectasia-mutated protein S1981 preceded activation of PKC and caspase-3. Constitutive SUMOylation facilitated 1% O 2 - or DFO-induced nuclear factor B transactivation, possibly via activation of genotoxic signaling cascade. In addition, we observed transient preservation of transepithelial electrical resistance during the early stage of hypoxia (1% O 2 ) as well as enhanced transepithelial electrical resistance recovery after prolonged hypoxia in SUMO-1-expressing cell monolayers. In conclusion, our results unveil a previously unrecognized mechanism by which SUMOylation and activation of ataxia-telangiectasia-mutated protein, PKC , caspase-3, and nuclear factor B signaling pathways modulate salivary adaptive responses to stress in cells exposed to either 1% O 2 or DFO.
Loading next page...
 
/lp/american-society-for-investigative-pathology/sumoylation-attenuates-sensitivity-toward-hypoxia-or-desferroxamine-WKS6ICre2F

You're reading a free preview. Sign up for a free trial to continue reading.

By signing up, you agree to DeepDyve's Terms of Service and Privacy Policy.

What content is in DeepDyve?

  • Read and share from thousands of the leading scholarly journals from Springer, Elsevier, Nature, IEEE, Wiley-Blackwell and more.
  • All the latest content is available, no embargo periods.

Rent Scholarly Articles?

  • Read the full article in your browser.
  • Access all of your rentals from the cloud anywhere you have an internet connection.
  • Beautiful reading experience – Full charts and figures, just like the PDF.
  • Read as much as you'd like - whenever you'd like.

Happy Users

“In one word renting from DeepDyve is FANTASTIC!!! ... 99% of the time I only need access to an article for a month or so, so renting the articles is perfect for me.”

Adam S.

“Thanks for a great service! For an unaffiliated science blogger like myself this is like a dream come true.”

Seppo P.

“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.

“Let me seize this opportunity and congratulate you on the service you are rendering to the scientific community.”

Joao B.