Abstract
Intravitreal injection of α-crystallin can promote axons from optic nerve regeneration after crushing in rats. We have previously demonstrated that α-crystallin can counteract the effect of myelin inhibitory factors and stimulate neurite growth. And a common crucial signaling event for myelin inhibitory factors is the activation of RhoA. To investigate whether α-crystallin counteracts the inhibitory effect of myelin inhibitory factors through regulation of RhoA/Rock signaling pathway, α-crystallin (10−4 g/L) was injected into rat vitreous at the time the optic nerve crushed. The RhoA protein activity and the expression of RhoA and Rock were evaluated after 3 days of optic nerve axotomy. Rock downstream effectors, phosphorylated cofilin, and phosphorylated myosin light chain were detected when retinal neurons were cultured for 3 days. Axonal regeneration and neurites growth of cultured cells were observed also. Our results showed that α-crystallin decreased the RhoA protein activity and the phosphorylation of both cofilin and myosin light chain, and promoted the axonal growth. However, the expression of RhoA and Rock was not affected by α-crystallin. These findings indicated that α-crystallin could counteract the effect of myelin inhibitory factors through the regulation of RhoA/Rock signaling pathway.
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Acknowledgments
The study is supported by grants from National Key Basic Scientific Research Project (973 Project) of China (2007CB512203), National Natural Science Foundation of China(grant no. 30872833), the Military 11th Five-year Project of China (grant no. 06G072), and Youth Innovation Fund of the Third Military Medical University (no. 32009XQN29). The authors thank Dr. T. FitzGibbon for the comments on previous drafts of the manuscript.
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Wang, Y.H., Wang, D.W., Wu, N. et al. Alpha-Crystallin Promotes Rat Axonal Regeneration Through Regulation of RhoA/Rock/Cofilin/MLC Signaling Pathways. J Mol Neurosci 46, 138–144 (2012). https://doi.org/10.1007/s12031-011-9537-z
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DOI: https://doi.org/10.1007/s12031-011-9537-z