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SHR Neuro Cancer Cardio Lipid

Themanns, M; Mueller, KM; Kessler, SM; Golob-Schwarzl, N; Mohr, T; Kaltenecker, D; Bourgeais, J; Paier-Pourani, J; Friedbichler, K; Schneller, D; Schlederer, M; Zebedin-Brandl, E; Terracciano, LM; Han, X; Kenner, L; Wagner, KU; Mikulits, W; Kozlov, AV; Heim, MH; Gouilleux, F; Haybaeck, J; Moriggl, R.
Hepatic Deletion of Janus Kinase 2 Counteracts Oxidative Stress in Mice.
Sci Rep. 2016; 6(4):34719-34719 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Authors Med Uni Graz:
Golob-Schwarzl Nicole
Haybäck Johannes
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Number of Figures: 6
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Abstract:
Genetic deletion of the tyrosine kinase JAK2 or the downstream transcription factor STAT5 in liver impairs growth hormone (GH) signalling and thereby promotes fatty liver disease. Hepatic STAT5 deficiency accelerates liver tumourigenesis in presence of high GH levels. To determine whether the upstream kinase JAK2 exerts similar functions, we crossed mice harbouring a hepatocyte-specific deletion of JAK2 (JAK2Δhep) to GH transgenic mice (GHtg) and compared them to GHtgSTAT5Δhep mice. Similar to GHtgSTAT5Δhep mice, JAK2 deficiency resulted in severe steatosis in the GHtg background. However, in contrast to STAT5 deficiency, loss of JAK2 significantly delayed liver tumourigenesis. This was attributed to: (i) activation of STAT3 in STAT5-deficient mice, which was prevented by JAK2 deficiency and (ii) increased detoxification capacity of JAK2-deficient livers, which diminished oxidative damage as compared to GHtgSTAT5Δhep mice, despite equally severe steatosis and reactive oxygen species (ROS) production. The reduced oxidative damage in JAK2-deficient livers was linked to increased expression and activity of glutathione S-transferases (GSTs). Consistent with genetic deletion of Jak2, pharmacological inhibition and siRNA-mediated knockdown of Jak2 led to significant upregulation of Gst isoforms and to reduced hepatic oxidative DNA damage. Therefore, blocking JAK2 function increases detoxifying GSTs in hepatocytes and protects against oxidative liver damage.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Fatty Liver - genetics
Fatty Liver - metabolism
Fatty Liver - pathology
Gene Deletion -
Glutathione Transferase - metabolism
Human Growth Hormone - genetics
Janus Kinase 2 - genetics
Lipid Metabolism -
Liver - metabolism
Liver - pathology
Male -
Mice -
Mice, Transgenic -
Oxidative Stress -
Reactive Oxygen Species - metabolism
Signal Transduction -

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