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ER-stress caused by accumulated intracistanal granules activates autophagy through a different signal pathway from unfolded protein response in exocrine pancreas cells of rats exposed to fluoride

机译:积累的鼻骨内颗粒引起的内质网应激通过与暴露于氟化物的大鼠外分泌胰腺细胞中未折叠的蛋白质反应不同的信号途径激活自噬

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摘要

In rat exocrine pancreas cells, fluoride treatment causes autophagy resulting from intracisternal granule accumulation. Excessive autophagy might promote a type of programmed cell death different from apoptosis. To clarify how fluoride-induced autophagy and subsequent cell death occurs, we investigated morphological and biochemical changes in exocrine pancreas cells of rats subcutaneously injected with NaF saline solution at 20 mg/kg dose twice daily for 4 days. Intracisternal granule, excessive autophagy and ribosomal degranulation were observed in fluoride-exposed cells, occasionally with necrotic changes. Fluoride-induced rER-stress increased eIF-2α phosphorylation and CHOP expression, but did not affect GRP78. Spliced XBP-1 expression was decreased in damaged cells. These findings indicate that rER-stress by intracisternal granule accumulation lead to autophagy in exocrine pancreas cells without UPR, suggesting that signal process of autophagy differs from that of UPR-apoptosis. It is likely that intense degranulation is a turning point that damaged cells change over from autophagy, cell-protective process, to cell-death process.
机译:在大鼠外分泌胰腺细胞中,氟化物处理会导致由于脑池内颗粒堆积而导致自噬。过度自噬可能会促进一种不同于细胞凋亡的程序性细胞死亡。为了阐明氟化物诱导的自噬和随后的细胞死亡是如何发生的,我们调查了皮下注射NaF盐溶液的大鼠外分泌胰腺细胞的形态和生化变化,每天两次,每天两次,剂量为20 mg / kg,剂量为4天。在暴露于氟化物的细胞中观察到了胸骨内颗粒,过度的自噬和核糖体脱粒,偶尔出现坏死性变化。氟化物诱导的rER胁迫增加eIF-2α磷酸化和CHOP表达,但不影响GRP78。剪接的XBP-1表达在受损细胞中减少。这些发现表明,没有UPR的外分泌胰腺细胞中,由脑池内颗粒积累引起的rER应激导致自噬,这表明自噬的信号过程不同于UPR凋亡的信号过程。强烈的脱粒可能是受损细胞从自噬,细胞保护过程转变为细胞死亡过程的转折点。

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