Department of Biological Sciences, Seton Hall University, 400 South Orange Avenue, South Orange, NJ 07079, USA.
Biomolecules. 2021 Oct 22;11(11):1567. doi: 10.3390/biom11111567.
Elevated level of palmitic acid (PA), a long-chain saturated fatty acid (SFA), is lipotoxic to many different types of cells including Neuro-2a (N2a) neuroblastoma cells. CD36 is a multifunctional membrane glycoprotein that acts as a fatty acid translocase (FAT) facilitating the transport of long-chain free fatty acids (FFAs) into cells, serves a fatty acid (FA) sensing function in areas including taste buds and the proximal gut, and acts as a scavenger receptor that binds to many ligands, including FAs, collagen, oxidized low-density lipoproteins, and anionic phospholipids. However, the involvement of CD36 in FA uptake and PA lipotoxicity in N2a cells remains unclear. In this study, we examined FA uptake in BSA- and PA-treated N2a cells and investigated the involvement of CD36 in FA uptake and PA lipotoxicity in N2a cells. Our data showed that PA treatment promoted FA uptake in N2a cells, and that treatment with sulfo-N-succinimidyl oleate (SSO), a CD36 inhibitor, significantly decreased FA uptake in BSA- and PA-treated N2a cells, and ameliorated PA-induced decrease of cell viability, decrease of diploid cells, and increase of tetraploid cells. We also found that CD36 knockdown significantly decreased FA uptake in both BSA- and PA-treated cells as compared to their corresponding wild-type controls, and dramatically attenuated PA-induced cell cycle defects in N2a cells. Our data suggest that CD36 may play a critical role in FA uptake and PA lipotoxicity in N2a cells. CD36 may therefore represent a regulatory target against pathologies caused by excess FAs.
棕榈酸（PA）水平升高，一种长链饱和脂肪酸（SFA），对包括Neuro-2a（N2a）神经母细胞瘤细胞在内的许多不同类型的细胞都具有脂毒性。CD36 是一种多功能膜糖蛋白，作为脂肪酸转运蛋白（FAT）发挥作用，促进长链游离脂肪酸（FFAs）进入细胞，在包括味蕾和近端肠道在内的区域发挥脂肪酸（FA）感应功能，并作为一种清道夫受体，与许多配体结合，包括 FA、胶原蛋白、氧化低密度脂蛋白和阴离子磷脂。然而，CD36 参与 N2a 细胞中的 FA 摄取和 PA 脂毒性仍不清楚。在这项研究中，我们研究了 BSA 和 PA 处理的 N2a 细胞中的 FA 摄取，并研究了 CD36 参与 N2a 细胞中的 FA 摄取和 PA 脂毒性的情况。我们的数据表明，PA 处理促进了 N2a 细胞中的 FA 摄取，而 CD36 抑制剂磺基-N-琥珀酰亚胺辛酯（SSO）的处理显著降低了 BSA 和 PA 处理的 N2a 细胞中的 FA 摄取，并改善了 PA 诱导的细胞活力下降、二倍体细胞减少和四倍体细胞增加。我们还发现，与相应的野生型对照相比，CD36 敲低显著降低了 BSA 和 PA 处理的细胞中的 FA 摄取，并显著减弱了 PA 诱导的 N2a 细胞周期缺陷。我们的数据表明，CD36 可能在 N2a 细胞中的 FA 摄取和 PA 脂毒性中发挥关键作用。因此，CD36 可能是针对由过量 FA 引起的病理学的调节靶点。
