Effect of PMA-induced protein kinase C activation on development and apoptosis in early zebrafish embryos

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• 作者：Jelena Hrubik^a ; Branka Glisic^a ; Dragana Samardzija^a ; Bojana Stanic^b ; Kristina Pogrmic-Majkic^a ; Svetlana Fa^a ; Nebojsa Andric^a ; ^{nebojsa.andric@dbe.uns.ac.rs" class="auth_mail" title="E-mail the corresponding author}
• 关键词：AMPRA-R ; alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor ; apaf1 ; apoptotic peptidase activating factor 1 ; bax ; bcl2-associated X protein ; bcl-2 ; B-cell lymphoma 2 ; casp3 ; caspase 3 ; casp9 ; caspase 9 ; cat ; catalase ; CNS ; central nervous system ; DAG ; diacylglycerol ; ef1α ; elongation factor 1α ; emx1 ; empty spiracles homeobox 1 ; Erk ; extracellular signal-regulated kinase ; GFX ; GF109203X ; protein kinase C inhibitor ; hpf ; hours post fertilization ; mdm2 ; mouse double minute 2 homolog (M
• 刊名：Comparative Biochemistry and Physiology, Part C
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：190
• 期：Complete
• 页码：24-31
• 全文大小：919 K

文摘

Protein kinase C (PKC) isoforms have been implicated in several key steps during early development, but the consequences of xenobiotic-induced PKC activation during early embryogenesis are still unknown. In this study, zebrafish embryos were exposed to a range of phorbol 12-myristate 13-acetate (PMA) concentrations (0–200 μg/L) at different time points after fertilization. Results showed that 200 μg PMA/L caused development of yolk bags, cardiac edema, slow blood flow, pulsating blood flow, slow pulse, elongated heart, lack of tail fins, curved tail, and coagulation. PMA exposure decreased survival rate of the embryos starting within the first 24 h and becoming more pronounced after prolonged exposure (96 h). PMA increased the number of apoptotic cells in the brain region as demonstrated by acridine orange staining and caused up-regulation of caspase 9 (casp9) and p53 up-regulated modulator of apoptosis (puma) mRNA in whole embryos. PMA caused oxidative stress in the embryos as demonstrated by decreased mRNA expression of catalase and superoxide dismutase 2. Inhibition of Pkc with GF109203X improved overall survival rate, reduced apoptosis in the brain and decreased expression of casp9 and puma in the PMA-exposed embryos. However, Pkc inhibition neither prevented development of deformities nor reversed oxidative stress in the PMA-exposed embryos. These data suggest that direct over-activation of Pkc during early embryogenesis of zebrafish is associated with apoptosis and decreased survival rate of the embryos.