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过氧化物酶体在小鼠内分泌和外分泌胰腺的出生后发育过程中表现出细胞类型和阶段特异性的蛋白质组成。

Peroxisomes during postnatal development of mouse endocrine and exocrine pancreas display cell-type- and stage-specific protein composition.

机构信息

Institute for Anatomy and Cell Biology, Medical Cell Biology, Justus Liebig -University, Aulweg 123, 35392, Giessen, Germany.

Institute for Medical Informatic, Justus Liebig University, Rudolf-Buchheim-Str. 6, 35392, Gießen, Germany.

出版信息

Cell Tissue Res. 2023 Jul;393(1):63-81. doi: 10.1007/s00441-023-03766-6. Epub 2023 May 1.

Abstract

Peroxisomal dysfunction unhinges cellular metabolism by causing the accumulation of toxic metabolic intermediates (e.g. reactive oxygen species, very -chain fatty acids, phytanic acid or eicosanoids) and the depletion of important lipid products (e.g. plasmalogens, polyunsaturated fatty acids), leading to various proinflammatory and devastating pathophysiological conditions like metabolic syndrome and age-related diseases including diabetes. Because the peroxisomal antioxidative marker enzyme catalase is low abundant in Langerhans islet cells, peroxisomes were considered scarcely present in the endocrine pancreas. Recently, studies demonstrated that the peroxisomal metabolism is relevant for pancreatic cell functionality. During the postnatal period, significant changes occur in the cell structure and the metabolism to trigger the final maturation of the pancreas, including cell proliferation, regulation of energy metabolism, and activation of signalling pathways. Our aim in this study was to (i) morphometrically analyse the density of peroxisomes in mouse endocrine versus exocrine pancreas and (ii) investigate how the distribution and the abundance of peroxisomal proteins involved in biogenesis, antioxidative defence and fatty acid metabolism change during pancreatic maturation in the postnatal period. Our results prove that endocrine and exocrine pancreatic cells contain high amounts of peroxisomes with heterogeneous protein content indicating that distinct endocrine and exocrine cell types require a specific set of peroxisomal proteins depending on their individual physiological functions. We further show that significant postnatal changes occur in the peroxisomal compartment of different pancreatic cells that are most probably relevant for the metabolic maturation and differentiation of the pancreas during the development from birth to adulthood.

摘要

过氧化物酶体功能障碍通过导致有毒代谢中间产物(例如活性氧、长链脂肪酸、植烷酸或类二十烷酸)的积累和重要脂质产物(例如 质体、多不饱和脂肪酸)的消耗,破坏细胞代谢,导致各种促炎和破坏性的病理生理状况,如代谢综合征和与年龄相关的疾病,包括糖尿病。由于过氧化物酶体抗氧化标志物酶过氧化氢酶在胰岛细胞中含量低,过氧化物酶体被认为在内分泌胰腺中很少存在。最近的研究表明,过氧化物酶体代谢与胰腺细胞功能有关。在出生后期间,细胞结构和代谢发生重大变化,以触发胰腺的最终成熟,包括细胞增殖、能量代谢调节和信号通路激活。我们在这项研究中的目的是:(i)形态学分析小鼠内分泌与外分泌胰腺中过氧化物酶体的密度;(ii)研究在出生后期间胰腺成熟过程中,参与生物发生、抗氧化防御和脂肪酸代谢的过氧化物酶体蛋白的分布和丰度如何变化。我们的结果证明,内分泌和外分泌胰腺细胞含有大量具有异质蛋白含量的过氧化物酶体,这表明不同的内分泌和外分泌细胞类型需要根据其各自的生理功能特定的一组过氧化物酶体蛋白。我们进一步表明,不同胰腺细胞的过氧化物酶体区室发生显著的出生后变化,这对于出生到成年期间胰腺的代谢成熟和分化可能是重要的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd47/10313850/aeee81474ed0/441_2023_3766_Fig1_HTML.jpg

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