RESUMEN
BACKGROUND: Humanin (HN) is an extensive neuroprotective peptide. This study aims to investigate the neuroprotective effects of HN on Calyculin A (CA)-induced neurotoxicities in cortical neurons and the underlying mechanism. METHODS: CA was added into the cultured cortical neurons to induce neurotoxicity. Cortical neurons were preincubated with HN which plays a protective role. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH), and Calcein-AM were applied to evaluate the neural insults. Caspase 3 signal and Tunnel were performed to test neural apoptosis. Western blot analysis was used to detect the expressions of phosphorylated tau. The corresponding kits were used to measure the contents of malondialdehyde (MDA) and superoxide dismutase (SOD), and the activity of PP2A, respectively. RESULTS: HN preincubation preserved cell viability, protected the neurons, alleviated oxidative stress, and reserved PP2A activity. It also blocked tau overphosphorylation at Ser199/202, Ser396, and Thr231 sites and protected neurons against CA-induced insults. CONCLUSION: These results suggest that HN may serve as a potential therapeutic agent to prevent the pathological changes induced by CA via modulating the activity of PP2A and oxidative stress in neurodegenerative diseases.
Asunto(s)
Carcinógenos/toxicidad , Corteza Cerebral/efectos de los fármacos , Péptidos y Proteínas de Señalización Intracelular/farmacología , Toxinas Marinas/toxicidad , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Fármacos Neuroprotectores/farmacología , Oxazoles/toxicidad , Estrés Oxidativo/efectos de los fármacos , Fosforilación/efectos de los fármacos , Proteína Fosfatasa 2/efectos de los fármacos , Proteínas tau/deficiencia , Animales , Animales Recién Nacidos , Células Cultivadas , Corteza Cerebral/citología , RatasRESUMEN
Previous researches have showed that HSP90AA is important in ovarian cancer, but the mechanism of HSP90AA is still unknown. This study aimed to investigate the role of the potential therapy target protein HSP90AA1 in ovarian cancer. The level of HSP90AA1 in ovarian cancer SKOV3 cell line was altered by RNAi and overexpression. Survival of these cell lines was investigated by tetrazolium-based assay and fluorescence-activated cell sorter (FACS). The chemosensitivity to cisplatin of the cell was also tested by FACS when HSP90AA1 was overexpressed. HSP90AA1 RNAi inhibited the proliferation of ovarian cancer SKOV3 cell line and increased the apoptosis. Furthermore, overexpression of HSP90AA1 decreased the chemosensitivity to cisplatin of SKOV3 cells and overexpression of HSP90AA1 could partially rescue the survival rate of SKOV3 cells which were treated with cisplatin. HSP90AA1 is required for the survival and proliferation of SKOV3 cells. High level of HSP90AA1 can increase chemoresistance to cisplatin of SKOV3 cells.