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Inês Araújo and Ana Isabel Santos publish on The Antioxid Redox Signal Journal

Inês Araújo and Ana Isabel Santos, CBMR researchers, published recently on the Antioxid Redox Signal Journal the article: “S-nitrosylation of Ras mediates nitric oxide dependent post-injury neurogenesis in a seizure model”.

Know more about the article here.

Abstract: Nitric oxide (NO) is involved in the upregulation of endogenous neurogenesis in the subventricular zone and in the hippocampus after injury. One of the main neurogenic pathways activated by NO is the ERK/MAPK pathway, downstream of the EGF receptor. However, the mechanism by which NO stimulates cell proliferation through activation of the ERK/MAPK pathway remains unknown, although p21Ras seems to be one of the earliest targets of NO. Here, we aimed to study the possible neurogenic action of NO by post-translational modification of p21Ras as a relevant target for early neurogenic events promoted by NO in neural stem cells (NSC).

Results: We show that NO caused S-nitrosylation of p21Ras in Cys118, which triggered downstream activation of the ERK/MAPK pathway and proliferation of NSC. Moreover, in cells overexpressing a mutant Ras in which Cys118 was replaced by a serine -C118S-, cells were insensitive to NO, and no increase in S-nitrosylation, in ERK phosphorylation or in cell proliferation were observed. We also show that, following seizures, in the presence of NO derived from inducible nitric oxide synthase, there was an increase in p21Ras cysteine modification concomitant with the previously described stimulation of proliferation in the dentate gyrus.

Innovation: Our work identifies p21Ras and its S-nitrosylation as an early target of NO during signaling events that lead to NSC proliferation and neurogenesis.

Conclusion: Our data highlight Ras S-nitrosylation as an early event leading to NSC proliferation, and may provide a target for NO-induced stimulation of neurogenesis with implications for brain repair.

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