Laboratoire du Métabolisme Moléculaire des Lipides, Centre de Recherches CERMO-FC, Département des Sciences Biologiques, Université du Québec à Montréal (UQAM), 141 av. du Président-Kennedy, Montréal, QC H2X 1Y4, Canada.
Laboratoire de Biologie Moléculaire, Département des Sciences Biologiques, Université du Québec à Montréal (UQAM), 141 av. du Président-Kennedy, Montréal, QC H2X 1Y4, Canada.
Int J Mol Sci. 2021 Apr 16;22(8):4118. doi: 10.3390/ijms22084118.
Apolipoprotein D (ApoD) is a secreted lipocalin associated with neuroprotection and lipid metabolism. In rodent, the bulk of its expression occurs in the central nervous system. Despite this, ApoD has profound effects in peripheral tissues, indicating that neural ApoD may reach peripheral organs. We endeavor to determine if cerebral ApoD can reach the circulation and accumulate in peripheral tissues. Three hours was necessary for over 40% of all the radiolabeled human ApoD (hApoD), injected bilaterally, to exit the central nervous system (CNS). Once in circulation, hApoD accumulates mostly in the kidneys/urine, liver, and muscles. Accumulation specificity of hApoD in these tissues was strongly correlated with the expression of lowly glycosylated basigin (BSG, CD147). hApoD was observed to pass through bEnd.3 blood brain barrier endothelial cells monolayers. However, cyclophilin A did not impact hApoD internalization rates in bEnd.3, indicating that ApoD exit from the brain is either independent of BSG or relies on additional cell types. Overall, our data showed that ApoD can quickly and efficiently exit the CNS and reach the liver and kidneys/urine, organs linked to the recycling and excretion of lipids and toxins. This indicated that cerebral overexpression during neurodegenerative episodes may serve to evacuate neurotoxic ApoD ligands from the CNS.
载脂蛋白 D（ApoD）是一种与神经保护和脂质代谢有关的分泌型脂联素。在啮齿动物中，其大部分表达发生在中枢神经系统。尽管如此，ApoD 在周围组织中仍具有深远的影响，这表明神经 ApoD 可能到达周围器官。我们努力确定大脑 ApoD 是否可以到达循环并在周围组织中积累。将放射性标记的人类 ApoD（hApoD）双侧注射后，需要 3 个小时才能使超过 40%的 hApoD 离开中枢神经系统（CNS）。一旦进入循环，hApoD 主要积聚在肾脏/尿液、肝脏和肌肉中。hApoD 在这些组织中的积累特异性与低糖基化 basigin（BSG，CD147）的表达强烈相关。观察到 hApoD 通过 bEnd.3 血脑屏障内皮细胞单层。然而，环孢素 A 并不影响 bEnd.3 中 hApoD 的内化率，表明 ApoD 从大脑中的排出要么独立于 BSG，要么依赖于其他细胞类型。总的来说，我们的数据表明，ApoD 可以快速有效地从 CNS 中排出，并到达肝脏和肾脏/尿液，这些器官与脂质和毒素的回收和排泄有关。这表明在神经退行性发作期间大脑的过度表达可能有助于从 CNS 中清除神经毒性的 ApoD 配体。
