Peroxisomes and Kidney Damage

by Radovan Vasko
Doctoral thesis
Date of Examination:2014-12-16
Date of issue:2014-12-12
Advisor:Prof. Dr. Hassan Dihazi
Referee:Prof. Dr. Hassan Dihazi
Referee:Prof. Dr. Michael Thumm
Persistent Address: http://dx.doi.org/10.53846/goediss-4825

 

 

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Abstract

English

This work examined (a) how the endotoxic stress affects peroxisomal function and autophagic degradation of peroxisomes-pexophagy, (b) how a superimposed dysfunction of lysosomes and pexophagy modifies responses to lipopolysaccharide, and (c) the mechanisms of peroxisomal contribution to renal injury. To accomplish this, we used lysosome-defective mice in vivo and primary endothelial cells in vitro, and compared the responses with wild-type littermates.  We demonstrated that pexophagy is a default response to endotoxic injury. However, when lysosomal dysfunction (a frequent companion of chronic diseases) is superimposed, recycling and functioning of peroxisomes are impaired, and an imbalance between hydrogen peroxide-generating β-oxidation and hydrogen peroxide-detoxifying catalase ensues, which ultimately results in peroxisomal burnout. Our data strongly suggest that pexophagy, a cellular mechanism per se, is essential in functional maintenance of peroxisomes during lipopolysaccharide exposure. Inhibition of pexophagy results in accumulation of impaired peroxisomes, redox disequilibrium, and aggravated renal damage.
Keywords: peroxisomes; pexophagy; endotoxic stress; renal damage
 
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