Protective role of integrin-linked kinase against oxidative stress and in maintenance of genomic integrity
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Michelle Im1,2,3 and Lina Dagnino1,2,3
1Department of Physiology and Pharmacology, The University of Western London, Ontario, Canada
2Lawson Health Research Institute, London, Ontario, Canada
3Children's Health Research Institute, London, Ontario, Canada
Lina Dagnino, email: [email protected]
Keywords: oxidative stress; epidermis; integrin-linked kinase
Received: September 27, 2017 Accepted: January 24, 2018 Published: February 07, 2018
The balance between the production of reactive oxygen species and activation of antioxidant pathways is essential to maintain a normal redox state in all tissues. Oxidative stress caused by excessive oxidant species generation can cause damage to DNA and other macromolecules, affecting cell function and viability. Here we show that integrin-linked kinase (ILK) plays a key role in eliciting a protective response to oxidative damage in epidermal cells. Inactivation of the Ilk gene causes elevated levels of intracellular oxidant species (IOS) and DNA damage in the absence of exogenous oxidative insults. In ILK-deficient cells, excessive IOS production can be prevented through inhibition of NADPH oxidase activity, with a concomitant reduction in DNA damage. Additionally, ILK is necessary for DNA repair processes following UVB-induced damage, as ILK-deficient cells show a significantly impaired ability to remove cyclobutane pyrimidine dimers following irradiation. Thus, ILK is essential to maintain cellular redox balance and, in its absence, epidermal cells become more susceptible to oxidative damage through mechanisms that involve IOS production by NADPH oxidase activity.
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