De Nunzio Valentina, Aloisio Caruso Emanuela, Centonze Matteo, Pinto Giuliano, Cofano Miriam, Saponara Ilenia, Notarnicola Maria
Laboratory of Nutritional Biochemistry, National Institute of Gastroenterology IRCCS "Saverio de Bellis", Castellana Grotte, Italy.
FEBS Open Bio. 2025 Mar;15(3):462-473. doi: 10.1002/2211-5463.13945. Epub 2024 Dec 10.
The condition of cellular senescence has specific features, including an altered lipid metabolism. Delta-9 desaturase (Δ9) catalyzes the conversion of saturated fatty acids, such as palmitic acid and stearic acid, into their monounsaturated forms, palmitoleic and oleic acid, respectively. Δ9 activity is important for most lipid functions, such as membrane fluidity, lipoprotein metabolism and energy storage. The present study aimed to investigate differences in the expression of Δ9 in senescence-induced pancreatic (MIA-PaCa-2 and PANC-1) and hepatic (Hepa-RG and HLF) cancer cell lines. Cellular senescence was induced by growing cells in the presence of the chemotherapic drug doxorubicin. Senescence status was determined by the senescence-associated beta-galactosidase activity assay kit combined with the p21 and senescence associated secretory phenotype protein assay. Δ9 was downregulated in all senescence-induced cell lines compared to control cells, in both the lipidomic analysis and when measuring protein levels via western blotting. Hence, our findings demonstrate that the study of membrane lipid composition and the expression levels of Δ9 could potentially form the basis for future applications investigating the state of cellular senescence.
细胞衰老状态具有特定特征，包括脂质代谢改变。Δ9去饱和酶（Δ9）催化饱和脂肪酸（如棕榈酸和硬脂酸）分别转化为它们的单不饱和形式，即棕榈油酸和油酸。Δ9活性对于大多数脂质功能（如膜流动性、脂蛋白代谢和能量储存）很重要。本研究旨在调查衰老诱导的胰腺癌细胞系（MIA-PaCa-2和PANC-1）和肝癌细胞系（Hepa-RG和HLF）中Δ9表达的差异。通过在化疗药物阿霉素存在的情况下培养细胞来诱导细胞衰老。衰老状态通过衰老相关β-半乳糖苷酶活性检测试剂盒结合p21和衰老相关分泌表型蛋白检测来确定。在脂质组学分析以及通过蛋白质印迹法测量蛋白质水平时，与对照细胞相比，所有衰老诱导的细胞系中Δ9均下调。因此，我们的研究结果表明，对膜脂质组成和Δ9表达水平的研究可能为未来研究细胞衰老状态的应用奠定基础。
