Oxidative stress has been shown play a role in damaging the tight junction in epithelial cells, as many literature suggest. However, in the most oxidative stress cell culture model, it is difficult to distinguish whether the damaged tight junction is due to intra-cellular or extra-cellular ROS. Anyone knows which plays the major role? Thanks
Accumulated ROS causes dysfunction of protein turnover by interrupting the ubiquitin-protesome degradation. Adhesion molecules such as beta-catenin, E-cadherin and CD44 need to be replaced with new synthesized proteins, thereby maintaining the epithelial cell characteristics with attachment to the basal membrane. Epithelial cells tend to express CD44 variant instead of CD44 standard due to the alternative splicing by ESRP1/2 RNA-binding proteins. CD44v-meditaed xCT promotes cysteine uptake, the essential substrate of reduced glutathione (GSH), one of the ROS scavengers.
In our experience we have found that MCF-7 cells (but not HaCaT) changed morphology of monolayer (contractions of the cells, rounding, but keeping cytoplasmic bridges between cells). I guess it could be indirect proofs of keeping tight junction during oxidative stress induced with UV-B.
Yes, especially famous to do this are peroxynitrite and hypochlorous acid. These can be exogenously applied by using chemical donors.
https://www.google.co.uk/#q=tight+junction%2C+hypochlorous+acid
https://www.google.co.uk/#q=tight+junction,+peroxynitrite
H2O2 has important effects as well:
https://www.google.co.uk/#q=tight+junction%2C+h2o2
To set up a model of endogenously induced ROS/RNS, you may try things like: LPS, TNF-alpha, hEGF, AngII. All are superoxide inducers, which lead to a cascade of secondary ROS/RNS production. The kinetics of NO production is different from that of superoxide. You need to check the literature, depending on the the inducers you choose.
High glucose, high osmolarity, high salt tension, physical shear are also possible inducers, with documentations.
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