Fig 6. SDS pancreas senescence is downstream of p53-dependent changes in protein synthesis.

A, Increased nuclei per acinar area (*P = 0.029, Wilcoxon Rank Sum Test) and B, decreased mean acinus diameter (**P = 0.0073 and NS = not significant, P = 0.142; unpaired, two-sided T-test) in Sbds ^P–/R126T; Trp53 ^–/–pancreas at 30 days of age. Error bars represent ±SEM; in boxplots, whiskers represent extreme values; circles, outliers. C, Coomassie and silver staining of pancreas lysate SDS-PAGE illustrated p53-dependent altered protein expression in the SDS pancreas (20 days of age, 6 μg total protein loaded). D, Immunoblotting confirmed that digestive enzymes were reduced in expression in the SDS pancreas, with expression of protease carboxypeptidase (Cpa1) increasing in a Trp53 ^–/–genetic background (3 weeks of age, 25 μg total protein loaded). Representative blots are shown. Associated densitometry, with expression relative to Gapdh, is shown in lower panels, Sbds ^P–/+ black, Sbds ^P–/R126T grey, horizontal lines indicate mean values. E, Restoration of zymogen granules (example, white arrowhead) with loss of p53 was observed by one week of age (electron micrographs). Scale bar represents 5 μm. F, Representative polysome traces illustrate restoration of 80S peak in mutants to levels similar to those of controls with loss of p53 (20 days of age, 79 μg RNA loaded, N = 4 (Trp53 ^+/–) and 3(Trp53 ^–/–)). P: polysomes.