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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:e126.)
© 2006 American Heart Association, Inc.

Letter to the Editor

Inhibition of Extracellular Signal–Regulated Kinase in Liver of Hyperhomocysteinemic Mice

Julien Hamelet

EA 3508, Université Paris 7-Denis Diderot

Karine Demuth

Service de Biochimie, Hopital Europeen Georges Pompidou

Jean-Maurice Delabar; Nathalie Janel

EA 3508, Université Paris 7-Denis Diderot, Paris, France

An extract of the first 250 words of the full text is provided, because this article has no abstract.

To the Editor:

We read with great interest the article by Woo et al,¹ reporting the involvement of cAMP-dependent protein kinase A (cAMP-PKA) signaling pathway in activation of the transcription factor cAMP-response element binding protein (CREB) during hyperhomocysteinemia in the liver. Hyperhomocysteinemia, defined as elevated homocysteine (Hcy) levels in blood, is not only associated with cardiovascular and cerebrovascular disorders, but is also accompanied by hepatic steatosis.² As CREB plays an important role in the expression of genes involved in lipid metabolism, the work of Woo et al¹ is of great importance to show the mechanism by which Hcy induces CREB activation. Among the signaling pathways important for activation of CREB, protein kinases such as PKA, extracellular signal regulated-kinase (ERK), and p38 mitogen-activating protein (p38 MAP) kinase are able to phosphorylate CREB leading to its activation.³ Woo et al¹ demonstrated, by incubation of hepatocytes with inhibitor of protein kinases, that Hcy-induced CREB activation is mediated by PKA signaling pathway, but not by ERK pathway or p38 MAP kinase pathway. These results are very intriguing because we have showed the involvement of ERK and PKA signaling pathways in the Hcy-induced CREB activation in an ex vivo model of hippocampal slices.⁴ As we have also shown an activation of ERK and the downstream nuclear target CREB in the hippocampus of cystathionine beta synthase (CBS)-deficient mice, a murine model of hyperhomocysteinemia,⁴ the present work was designed to investigate whether activation of ERK also occurs in liver of CBS-deficient mice.

Heterozygous CBS-deficient (Cbs^+/–) . . . [Full Text of this Article]