Roumes Hélène, Brossaud Julie, Lemelletier Aloïs, Moisan Marie-Pierre, Pallet Véronique, Redonnet Anabelle, Corcuff Jean-Benoît
INRA, Nutrition et neurobiologie intégrée, UMR 1286, 33076 Bordeaux, France; University Bordeaux, Nutrition et neurobiologie intégrée, UMR 1286, 33076 Bordeaux, France.
University Bordeaux, Nutrition et neurobiologie intégrée, UMR 1286, 33076 Bordeaux, France; Laboratoire d'Hormonologie, Service de médecine nucléaire, CHU Bordeaux, 33604 Pessac, France.
Int J Biochem Cell Biol. 2016 Feb;71:102-110. doi: 10.1016/j.biocel.2015.12.014. Epub 2015 Dec 31.
A chronic excess of glucocorticoids elicits deleterious effects in the hippocampus. Conversely, retinoic acid plays a major role in aging brain plasticity. As synaptic plasticity depends on mechanisms related to cell morphology, we investigated the involvement of retinoic acid and glucocorticoids in the remodelling of the HT22 neurons actin cytoskeleton. Cells exhibited a significantly more elongated shape with retinoic acid and a rounder shape with dexamethasone; retinoic acid reversed the effects of dexamethasone. Actin expression and abundance were unchanged by retinoic acid or dexamethasone but F-actin organization was dramatically modified. Indeed, retinoic acid and dexamethasone increased (70 ± 7% and 176 ± 5%) cortical actin while retinoic acid suppressed the effect of dexamethasone (90 ± 6%). Retinoic acid decreased (-22 ± 9%) and dexamethasone increased (134 ± 16%) actin stress fibres. Retinoic acid also suppressed the effect of dexamethasone (-21 ± 7%). Spectrin is a key protein in the actin network remodelling. Its abundance was decreased by retinoic acid and increased by dexamethasone (-21 ± 11% and 52 ± 10%). However, retinoic acid did not modify the effect of dexamethasone (48 ± 7%). Calpain activity on spectrin was increased by retinoic acid and decreased by dexamethasone (26 ± 14% and -57 ± 5%); retinoic acid mildly but significantly modified the effect of dexamethasone (-44 ± 7%). The calpain inhibitor calpeptin suppressed the effects of retinoic acid and dexamethasone on cell shape and actin stress fibres remodelling but did not modify the effects on cortical actin. Retinoic acid and dexamethasone have a dramatic but mainly opposite effect on actin cytoskeleton remodelling. These effects originate, at least partly, from calpain activity.
长期过量的糖皮质激素会对海马体产生有害影响。相反，视黄酸在衰老大脑可塑性中起主要作用。由于突触可塑性取决于与细胞形态相关的机制，我们研究了视黄酸和糖皮质激素在HT22神经元肌动蛋白细胞骨架重塑中的作用。视黄酸处理的细胞呈现出明显更长的形态，而地塞米松处理的细胞则更圆；视黄酸可逆转地塞米松的作用。视黄酸或地塞米松对肌动蛋白的表达和丰度没有影响，但F-肌动蛋白的组织发生了显著改变。事实上，视黄酸和地塞米松增加了（分别为70±7%和176±5%）皮质肌动蛋白，而视黄酸抑制了地塞米松的作用（90±6%）。视黄酸减少了（-22±9%）而地塞米松增加了（134±16%）肌动蛋白应激纤维。视黄酸也抑制了地塞米松的作用（-21±7%）。血影蛋白是肌动蛋白网络重塑中的关键蛋白。其丰度视黄酸处理后降低，地塞米松处理后升高（分别为-21±11%和52±10%）。然而，视黄酸并未改变地塞米松的作用（48±7%）。视黄酸增加而地塞米松降低了血影蛋白上的钙蛋白酶活性（分别为26±14%和-57±5%）；视黄酸轻微但显著地改变了地塞米松的作用（-44±7%）。钙蛋白酶抑制剂钙肽素抑制了视黄酸和地塞米松对细胞形态和肌动蛋白应激纤维重塑的影响，但未改变对皮质肌动蛋白的影响。视黄酸和地塞米松对肌动蛋白细胞骨架重塑有显著但主要相反的作用。这些作用至少部分源于钙蛋白酶活性。
