Cre-Mediated Stress Affects Sirtuin Expression Levels, Peroxisome Biogenesis and Metabolism, Antioxidant and Proinflammatory Signaling Pathways

• DOI: 10.1371/journal.pone.0041097
• Publication Date: 2012-07-20T05:36:19Z
• Authors: Yu Xiao; Srikanth Karnati; Guofeng Qian; Anca Nenicu; Wei Fan; Svetlin Tchatalba...; Anita Höland; Hamid Hossain; Florian Guillou; Georg H. Lüers; Eveline Baumgart-...
• Keywords: Proinflammatory cytokine; SOD2

Cre-mediated excision of loxP sites is widely used in mice to manipulate gene function a tissue-specific manner. To analyze phenotypic alterations related Cre-expression, we have AMH-Cre-transgenic as model system. Different Cre expression levels were obtained by investigation C57BL/6J wild type well heterozygous and homozygous AMH-Cre-mice. Our results indicate that Cre-expression itself Sertoli cells already has led oxidative stress lipid peroxidation (4-HNE lysine adducts), inducing PPARα/γ, peroxisome proliferation biogenesis (PEX5, PEX13 PEX14) metabolic proteins (ABCD1, ABCD3, MFP1, thiolase B, catalase). In addition the strong catalase increase, NRF2- FOXO3-mediated antioxidative response (HMOX1 endoplasmic reticulum mitochondrial SOD2) NF-κB activation noted. TGFβ1 proinflammatory cytokines like IL1, IL6 TNFα upregulated stress-related signaling pathways induced. cell mRNA-microarray analysis revealed an increase TNFR2-signaling components. 53BP1 recruitment for DNA repair genes p53 elevated ones sirtuin deacetylases affected (SIRT 1, 3-7) cells. Under chronic damage conditions downregulation Sirt1 was observed, suggesting decrease this important coordinator between might induce repression release major transcription factors regulating cytokine-mediated pathways. Indeed, caspase-3 activated increased germ apoptosis paracrine effects. conclusion, observed wide stress-induced effects suggest it essential use correct control animals (Cre/Wt) with matched differentiate specific gene-knock out-mediated