Burn-Induced Apoptosis in the Livers of Aged Mice Is Associated With Caspase Cleavage of Bcl-xL

烧伤引起的老年小鼠肝脏细胞凋亡与 Bcl-xL 的 Caspase 裂解有关

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作者:Israel Muro, Andrea C Qualman, Elizabeth J Kovacs, Juan-Pablo Idrovo

Conclusions

Livers of aged mice exhibited different apoptotic processes compared to those of young mice early after burn injury. Collectively, burn-induced liver apoptosis in aged mice compromises hepatic serum protein production.

Methods

We compared the protein and gene expression levels in young and aged mice after a 15% total-body-surface-area burn. Liver and serum samples were collected at different time points after injury.

Results

Caspase-9 expression in liver tissue was downregulated by 47% in young animals and upregulated by 62% in aged animals 9 h postburn (P < 0.05). The livers of aged mice showed a Bcl-extra-large (Bcl-xL) transcription increase only after 6 h; however, the livers of young mice exhibited 4.3-fold, 14.4-fold, and 7.8-fold Bcl-xL transcription increases at 3, 6, and 9 h postburn, respectively (P < 0.05). The livers of young mice showed no changes in Caspase-9, Caspase-3, or Bcl-xL protein levels during the early postburn period. In contrast, the livers of aged mice contained cleaved caspase-9, reduced full-length caspase-3, and an accumulation of ΔN-Bcl-x at 6 and 9 h postburn (P < 0.05). p21 expression decreased in aged mice; however, it was significantly increased in the liver tissue of young mice postburn (P < 0.05). Serum amyloid A1 and serum amyloid A2 serum protein levels were 5.2- and 3.1-fold higher in young mice than in aged mice, respectively, at 6 and 9 h postburn (P < 0.05). Conclusions: Livers of aged mice exhibited different apoptotic processes compared to those of young mice early after burn injury. Collectively, burn-induced liver apoptosis in aged mice compromises hepatic serum protein production.

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