| Autor: |
Yubin Wang, Dulce Lopez, Pinakin Gunvant Davey, D. Joshua Cameron, Katherine Nguyen, Jennifer Tran, Elizabeth Marquez, Yan Liu, Xiaoning Bi, Michel Baudry |
| Jazyk: |
angličtina |
| Rok vydání: |
2016 |
| Předmět: |
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| Zdroj: |
Neurobiology of Disease, Vol 93, Iss , Pp 121-128 (2016) |
| Druh dokumentu: |
article |
| ISSN: |
1095-953X |
| DOI: |
10.1016/j.nbd.2016.05.007 |
| Popis: |
Calpain has been shown to be involved in neurodegeneration, and in particular in retinal ganglion cell (RGC) death resulting from increased intraocular pressure (IOP) and ischemia. However, the specific roles of the two major calpain isoforms, calpain-1 and calpain-2, in RGC death have not been investigated. Here, we show that calpain-1 and calpain-2 were sequentially activated in RGC dendrites after acute IOP elevation. By combining the use of a selective calpain-2 inhibitor (C2I) and calpain-1 KO mice, we demonstrated that calpain-1 activity supported survival, while calpain-2 activity promoted cell death of RGCs after IOP elevation. Calpain-1 activation cleaved PH domain and leucine-rich repeat protein phosphatase 1 (PHLPP1) and activated the Akt pro-survival pathway, while calpain-2 activation cleaved striatal-enriched protein tyrosine phosphatase (STEP) and activated STEP-mediated pro-death pathway in RGCs after IOP elevation. Systemic or intravitreal C2I injection to wild-type mice 2 h after IOP elevation promoted RGC survival and improved visual function. Our data indicate that calpain-1 and calpain-2 play opposite roles in high IOP-induced ischemic injury and that a selective calpain-2 inhibitor could prevent acute glaucoma-induced RGC death and blindness. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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