Theys Nicolas, Clippe André, Bouckenooghe Thomas, Reusens Brigitte, Remacle Claude
Laboratory of Cell Biology, Institute of Life Sciences, Université Catholique de Louvain, Louvain-la-Neuve, Belgium.
PLoS One. 2009 Jul 1;4(7):e6110. doi: 10.1371/journal.pone.0006110.
Islets from adult rat possess weak antioxidant defense leading to unbalance between superoxide dismutase (SOD) and hydrogen peroxide-inactivating enzymatic activities, catalase (CAT) and glutathione peroxidase (GPX) rending them susceptible to oxidative stress. We have shown that this vulnerability is influenced by maternal diet during gestation and lactation.
METHODOLOGY/PRINCIPAL FINDINGS: The present study investigated if low antioxidant activity in islets is already observed at birth and if maternal protein restriction influences the development of islet antioxidant defenses. Rats were fed a control diet (C group) or a low protein diet during gestation (LP) or until weaning (LPT), after which offspring received the control diet. We found that antioxidant enzymatic activities varied with age. At birth and after weaning, normal islets possessed an efficient GPX activity. However, the antioxidant capacity decreased thereafter increasing the potential vulnerability to oxidative stress. Maternal protein malnutrition changed the antioxidant enzymatic activities in islets of the progeny. At 3 months, SOD activity was increased in LP and LPT islets with no concomitant activation of CAT and GPX. This unbalance could lead to higher hydrogen peroxide production, which may concur to oxidative stress causing defective insulin gene expression due to modification of critical factors that modulate the insulin promoter. We found indeed that insulin mRNA level was reduced in both groups of malnourished offspring compared to controls. Analyzing the expression of such critical factors, we found that c-Myc expression was strongly increased in islets from both protein-restricted groups compared to controls.
Modification in antioxidant activity by maternal low protein diet could predispose to pancreatic islet dysfunction later in life and provide new insights to define a molecular mechanism responsible for intrauterine programming of endocrine pancreas.
成年大鼠胰岛的抗氧化防御能力较弱，导致超氧化物歧化酶（SOD）与过氧化氢灭活酶活性（过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GPX））之间失衡，使其易受氧化应激影响。我们已经表明，这种易感性受妊娠和哺乳期母体饮食的影响。
方法/主要发现：本研究调查了胰岛中低抗氧化活性在出生时是否已被观察到，以及母体蛋白质限制是否会影响胰岛抗氧化防御的发育。大鼠在妊娠期间（LP组）或直至断奶（LPT组）喂食对照饮食（C组）或低蛋白饮食，之后子代接受对照饮食。我们发现抗氧化酶活性随年龄变化。在出生时和断奶后，正常胰岛具有高效的GPX活性。然而，此后抗氧化能力下降，增加了对氧化应激的潜在易感性。母体蛋白质营养不良改变了子代胰岛中的抗氧化酶活性。在3个月时，LP组和LPT组胰岛中的SOD活性增加，而CAT和GPX没有伴随激活。这种失衡可能导致过氧化氢产生增加，这可能会导致氧化应激，由于调节胰岛素启动子的关键因子的修饰而导致胰岛素基因表达缺陷。我们确实发现，与对照组相比，两组营养不良子代的胰岛素mRNA水平均降低。分析这些关键因子的表达，我们发现与对照组相比，两个蛋白质限制组的胰岛中c-Myc表达均强烈增加。
母体低蛋白饮食对抗氧化活性的改变可能使个体在生命后期易患胰岛功能障碍，并为确定负责内分泌胰腺宫内编程的分子机制提供新的见解。
