Alternations of 14-3-3 theta and beta Protein Levels in Brain During Experimental Sepsis

作者：Memos Nikolaos^*; Kataki Agapi; Chatziganni Emmy; Nikolopoulou Marilena; Skoulakis Euthimios; Consoulas Christos; Zografos George; Konstadoulakis Manousos

来源：Journal of Neuroscience Research, 2011, 89(9): 1409-1418.

DOI：10.1002/jnr.22673

• apoptosis
• neuronal cell fate
• infection
• rat brain
• phosphoproteins

The 14-3-3 family members play a crucial role in the determination of cell fate, exerting their antiapoptotic activity through directly interfering with the critical function of the mitochondrial core proapoptotic machinery. Dimerization of 14-3-3 is vital for the interaction with many of its client proteins and is regulated by phosphorylation. In a previous study, we observed time-dependent neuronal apoptosis during sepsis. Therefore, in the present study, we sought to evaluate the expression of 14-3-3 theta and beta isoforms in septic brain and their association with apoptosis. Sepsis was induced by a CLP model in Wistar rats that were sacrificed at predefined time points. Flow cytometric analysis showed a sepsis-induced, time-dependent alteration of 14-3-3 theta and beta isoforms in both Neun(+) and GFAP(+) cells. 14-3-3 theta was linearly correlated with apoptosis, and stratified analysis for alive and apoptotic neuronal cells demonstrated a gradual down-regulation of theta isoform in alive neurons and astrocytes. The phospho-P38 (pP38) MAP kinase levels were altered in a time-dependent manner during sepsis, presenting a peak at 6 hr post-CLP. A significant correlation between the two isoforms of 14-3-3 was observed in septic rats, with the theta isoform predominant at all time points. The hippocampus, Purkinje cells, and glia-like cells showed intense immunohistochemical reactivity for 14-3-3 theta isoform, whereas the choroid plexus showed constantly increased beta isoform expression. Our results showed that sepsis alters the expression of both 14-3-3 theta and beta isoforms in a time-, cell-, and topography-dependent manner.

• 出版日期2011-9