PACAP protects neuronal PC12 cells from the cytotoxicity of human prion protein fragment 106–126
[摘要] Misfolding of the prion protein yields amyloidogenic isoforms, and it shows exacerbating neuronal damage in neurodegenerative disorders including prion diseases. Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) potently stimulate neuritogenesis and survival of neuronal cells in the central nervous system. Here, we tested these neuropeptides on neurotoxicity in PC12 cells induced by the prion protein fragment 106–126 [PrP (106–126)]. Concomitant application of neuropeptide with PrP(106–126) (5×10−5 M) inhibited the delayed death of neuron-like PC12 cells. In particular, PACAP27 inhibited the neurotoxicity of PrP(106–126) at low concentrations (>10−15 M), characterized by the deactivation of PrP(106–126)-stimulated caspase-3. The neuroprotective effect of PACAP27 was antagonized by the selective PKA inhibitor, H89, or the MAP kinase inhibitor, U0126. These results suggest that PACAP27 attenuates PrP(106–126)-induced delayed neurotoxicity in PC12 cells by activating both PKA and MAP kinases mediated by PAC1 receptor.
[发布日期] [发布机构]
[效力级别] [学科分类] 生物化学/生物物理
[关键词] Pituitary adenylate cyclase-activating polypeptide;Vasoactive intestinal peptide;PC12 cell;Prion protein-106–126;Caspase;Circular dichroism;Ac-DEVD-CHO;acetyl-Asp-Glu-Val-Asp-1-al;CD;circular dichroism;db-cAMP;dibutyryl-cAMP;DMEM;Dulbecco's modified Eagle's medium;H89;N-(2-[p-bromocinnamylamino]ethyl)-5-isoquinolinesulfonamide;MAP;mitogen-activated protein;Myr-ψPKC;myristoyl-Gly-Arg-Arg-Asn-Ala-Ile-His-Asp-Ile;LDH;lactate dehydrogenase;PACAP;pituitary adenylate cyclase activating polypeptide;PKA;protein kinase A;PKC;protein kinase C;PrP;prion protein;PrPc;native cellular prion protein;PrPsc;scrapie isoform of prion protein;TPA;12-O-tetradecanoyl-phorbol-13-acetate;U0126;bis[amino[(2-aminophenyl)thio]methylene]butanedinitrile;VIP;vasoactive intestinal peptide;WST-8;4-[3-(2-methoxy-4-nitrophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1;3-benzene disulfonate sodium salt;Z-VAD-FMK;N-benzyloxycarbonyl-Val-Ala-Asp(O-Me) fluoromethyl ketone [时效性]
