Pretreatment of human retinal pigment epithelial cells with sterculic acid forestalls fenretinide-induced apoptosis.
Pretreatment of human retinal pigment epithelial cells with sterculic acid forestalls fenretinide-induced apoptosis.
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用固定酸防止芬雷丁蛋白诱导的凋亡对人视网膜色素上皮细胞进行预处理。
DOI：
10.1038/s41598-022-26383-9
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发表时间：
2022-12-23
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
饱和脂肪酸与单不饱和脂肪酸的比例被认为在许多细胞功能中起关键作用，其由硬脂酰辅酶A去饱和酶（SCD）调节，所述硬脂酰辅酶A去饱和酶是单不饱和脂肪酸生物合成中的限速酶。以前，我们观察到减少SCD蛋白和酶活性诱导的细胞凋亡fenretinide，维甲酸的合成类似物，在人视网膜色素上皮（RPE）细胞系ARPE-19。在这里，我们研究了预处理ARPE-19与sterculic酸，SCD的环丙烯脂肪酸抑制剂，防止芬维A胺诱导的细胞凋亡的影响，SCD在细胞增殖和凋亡中的作用。我们发现，sterculic酸预处理防止芬维A胺诱导的细胞凋亡的细胞形态，活力和caspase-3激活的变化所示的影响。内质网（ER）相关蛋白的分析表明，sterculic酸预处理减少了fenretinide诱导的血红素加氧酶-1，ATF 3和GADD 153表达的上调，这些表达响应于活性氧（ROS）的产生。在抑制黄嘌呤氧化酶（XDH）方面，Sterculic acid与别嘌呤醇一样有效，这可能在降低XDH在芬维A胺诱导的ROS生成中的潜在作用方面发挥作用。Sterculic acid预处理也导致SOD 2 mRNA表达的减少。与神经酰胺相比，二氢神经酰胺的积累和活性氧的产生表明，非神经酰胺依赖性途径介导了芬维A胺诱导的细胞凋亡，而活性氧的介导是通过激活NF-κ Bp 50和NF-κ Bp 65下游信号级联反应来证实的。其预防作用进一步表明了后者的抗氧化/抗炎作用。综上所述，我们的研究结果表明，胖大海酸预处理可以减轻ROS介导的芬维A胺诱导的细胞凋亡。因此，胖大海酸可作为一种潜在的抗氧化剂和治疗剂。这些影响可能是独立的SCD活动的影响。
The ratio of saturated to monounsaturated fatty acids, thought to play a critical role in many cellular functions, is regulated by stearoyl-CoA desaturase (SCD), a rate-limiting enzyme in the biosynthesis of monounsaturated fatty acids. Previously, we observed a decrease in both SCD protein and enzymatic activity in apoptosis induced by fenretinide, a synthetic analog of retinoic acid, in the human retinal pigment epithelial (RPE) cell line ARPE-19. Here, we investigated the effect of pretreating ARPE-19 with sterculic acid, a cyclopropenoic fatty acid inhibitor of SCD, on preventing fenretinide-induced apoptosis, given the role of SCD in cell proliferation and apoptosis. We show that sterculic acid pretreatment prevents the effects of fenretinide-induced apoptosis shown by changes in cell morphology, viability, and caspase-3 activation. Analysis of endoplasmic reticulum (ER)-associated proteins shows that sterculic acid pretreatment reduced the fenretinide-induced upregulation of heme oxygenase-1, ATF3 and GADD153 expression that are in response to reactive oxygen species (ROS) generation. Sterculic acid is as effective as allopurinol in inhibition of xanthine oxidase (XDH), and this may play a role in reducing the potential role of XDH in fenretinide-induced ROS generation. Sterculic acid pretreatment also results in a reduction in SOD2 mRNA expression. Dihydroceramide accumulation, compared to ceramide, and ROS generation indicate that a ceramide-independent pathway mediates fenretinide-induced apoptosis, and ROS mediation is borne out by activation of the NF-κBp50 and NF-κBp65 downstream signaling cascade. Its prevention by sterculic acid pretreatment further indicates the latter’s antioxidant/anti-inflammatory effect. Taken together, our results suggest that sterculic acid pretreatment can mitigate ROS-mediated fenretinide-induced apoptosis. Thus, sterculic acid may serve as a potential antioxidant and therapeutic agent. These effects may be independent of its effects on SCD activity.
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影响因子：
5.6
作者：
Samuel, William;Kutty, R. Krishnan;Duncan, Todd;Vijayasarathy, Camasamudram;Kuo, Bryan C.;Chapa, Krysten M.;Redmond, T. Michael
通讯作者：
Redmond, T. Michael
影响因子：
6.2
作者：
Dillon, Roslyn;Greig, Michael J.;Bhat, B. Ganesh
通讯作者：
Bhat, B. Ganesh
DOI：
10.1016/j.bbamcr.2005.12.009
发表时间：
2006-02-01
影响因子：
5.1
作者：
Dymkowska, D;Szczepanowska, J;Wojtczak, L
通讯作者：
Wojtczak, L
影响因子：
4.2
作者：
Hains, BC;Yucra, JA;Hulsebosch, CE
通讯作者：
Hulsebosch, CE
硬脂酰辅酶A去饱和酶1通过促进神经酰胺合成介导结直肠癌细胞凋亡
影响因子：
4.6
作者：
Chen L;Ren J;Yang L;Li Y;Fu J;Li Y;Tian Y;Qiu F;Liu Z;Qiu Y
通讯作者：
Qiu Y