Hop/STI1 modulates retinal proliferation and cell death independent of PrPC.
Hop/STI1 is a co-chaperone adaptor protein for Hsp70/Hsp90 complexes. Hop/STI1 is found extracellularly and modulates cell death and differentiation through interaction with the prion protein (PrP(C)). Here, we investigated the expression of hop/STI1 and its role upon cell proliferation and cell death in the developing retina. Hop/STI1 is more expressed in developing rat retina than in the mature tissue. Hop/STI1 blocks retinal cell death in the neuroblastic layer (NBL) in a PrP(C) dependent manner, but failed to protect ganglion cells against axotomy-induced cell death. An antibody raised against hop/STI1 (alpha-STI1) blocked both ganglion cell and NBL cell death independent of PrP(C). cAMP/PKA, ERK, PI3K and PKC signaling pathways were not involved in these effects. Hop/STI1 treatment reduced proliferation, while alpha-STI1 increased proliferation in the developing retina, both independent of PrP(C). We conclude that hop/STI1 can modulate both proliferation and cell death in the developing retina independent of PrP(C).
Arruda-Carvalho
Maithe
M
Universidade Federal do Rio de Janeiro (UFRJ), Instituto de Biofísica da UFRJ, Centro de Ciências da Saúde, bloco G, G2-019 Cidade Universitária, 21941-902, Rio de Janeiro, Brazil.
Njaine
Brian
B
Silveira
Mariana S
MS
Linden
Rafael
R
Chiarini
Luciana B
LB
D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000494:pharmacology; D016923:Cell Death; D049109:Cell Proliferation / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018621:PrPC Proteins / Q000378:metabolism; D051381:Rats; D012160:Retina / Q000166:cytology* / Q000187:drug effects / Q000196:embryology; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000187:drug effects
D000906:Antibodies; D006360:Heat-Shock Proteins; D018621:PrPC Proteins; C489791:Stip1 protein, mouse; C489790:Stip1 protein, rat