Ischemic stroke is a major composition of
cerebrovascular disease, seriously threatening to human health in the world.
Activin A (ActA), belonging to
transforming growth factor-beta (TGF-β) super family, plays an important role in the hypoxic-ischemic
brain injury through ActA/Smads pathway. While as an essential phosphorylation assistor in TGF-β signaling, the functions and mechanisms of smad anchor for receptor activation (SARA) in ischemic
brain injury remain poorly understood. To solve this problem and explore the
pathological processes of
ischemic stroke, we used an
Oxygen-
Glucose deprivation (OGD) model in
nerve growth factor-induced differentiated rattus PC12
pheochromocytoma cells and down regulated the expressions of SARA by RNA interference technology. Our results showed that the repression of SARA before OGD exposure reduced the expressions of Smad2, 3, 4
mRNA and the phosphorylation rate of
Smad2 protein, but it did not affect the
mRNA expressions of Smad7. After OGD treatment, ActA/Smads pathway was activated and the expression of SARA in the SARA pre-repression group was significantly up-regulated. The pre-repression of SARA increased the sensitivities of nerve-like cells to OGD damage. Moreover, the
mRNA expression of Smad7 which was supposed to participate in the negative feedback of ActA/Smads pathway was also elevated due to OGD injury. Taken together, these results suggest a positive role of SARA in assisting the phosphorylation of Smad2 and maintaining the neuron protective effect of ActA/Smads pathway.