Effect of hyperhomocysteinemia on the protein kinase DYRK1A in liver of mice.
Hyperhomocysteinemia due to cystathionine beta synthase (CBS)-deficiency confers diverse clinical manifestations, notably liver diseases. Even if hyperhomocysteinemia in liver of CBS-deficient mice, a murine model of hyperhomocysteinemia, promotes mitochondrial oxidative stress and pro-apoptotic signals, protective signals may counteract these pro-apoptotic signals, leading to chronic inflammation. As DYRK1A, a serine/threonine kinase, has been described as a candidate antiapoptotic factor, we have analyzed the expression of DYRK1A in liver of CBS-deficient mice. We found that DYRK1A protein level was reduced in liver of CBS-deficient mice, which was not observed at the gene expression level. Moreover, the use of primary hepatocytes/Kupffer cells co-culture showed that degradation of DYRK1A induced by hyperhomocysteinemia requires calpain activation. Our results demonstrate a deleterious effect of hyperhomocysteinemia on DYRK1A protein expression, and emphasize the role of hyperhomocysteinemia on calpain activation.
Hamelet
Julien
J
EA 3508 - case 7104, Univ Paris Diderot, 75205 Paris cedex 13, France.
Noll
Christophe
C
Ripoll
Clémentine
C
Paul
Jean-Louis
JL
Janel
Nathalie
N
Delabar
Jean-Maurice
JM
D000818:Animals; D002154:Calpain / Q000378:metabolism; D018920:Coculture Techniques; D003541:Cystathionine beta-Synthase / Q000235:genetics; D004195:Disease Models, Animal; D004789:Enzyme Activation; D006023:Glycoproteins / Q000494:pharmacology; D022781:Hepatocytes / Q000201:enzymology; D020138:Hyperhomocysteinemia / Q000201:enzymology* / Q000235:genetics; D007728:Kupffer Cells / Q000201:enzymology; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D000097603:Dyrk Kinases
D002154:Calpain; D003541:Cystathionine beta-Synthase; D006023:Glycoproteins; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D000097603:Dyrk Kinases; C039304:calpain inhibitors