Medina José M, Tabernero Arantxa
Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Salamanca, Doctores de la Reina s/n, 37007 Salamanca, Spain.
J Physiol Paris. 2002 Apr-Jun;96(3-4):265-71. doi: 10.1016/s0928-4257(02)00015-3.
Unlike in the adult brain, the newborn brain specifically takes up serum albumin during the postnatal period, coinciding with the stage of maximal brain development. Here we shall summarize our knowledge about the role played by albumin in brain development. The role of this protein in brain development is intimately related to its ability to carry fatty acids. Thus, albumin stimulates oleic acid synthesis by astrocytes from the main metabolic substrates available during brain development. Astrocytes internalize albumin in vesicle-like structures by receptor-mediated endocytosis, which is followed by transcytosis, including passage through the endoplasmic reticulum (ER). The presence of albumin in the ER activates the sterol regulatory element-binding protein-1 (SREBP-1) and increases stearoyl-CoA 9-desaturase (SCD) mRNA, the key enzyme in oleic acid synthesis. Oleic acid released by astrocytes is used by neurons for the synthesis of phospholipids and is specifically incorporated into growth cones. In addition, oleic acid promotes axonal growth, neuronal clustering, and the expression of the axonal growth associated protein, GAP-43. All of these observations indicate neuronal differentiation. The effect of oleic acid on GAP-43 synthesis is brought about by the activation of protein kinase C. The expression of GAP-43 is significantly increased by the presence of albumin in neurons co-cultured with astrocytes, indicating that neuronal differentiation takes place by the presence of oleic acid synthesized and released by astrocytes in situ. In conclusion, during brain development the presence of albumin could play an important role by triggering the synthesis and release of oleic acid by astrocytes, thereby inducing neuronal differentiation.
与成人大脑不同，新生大脑在出生后特定时期会摄取血清白蛋白，这与大脑发育的高峰期相吻合。在此，我们将总结关于白蛋白在大脑发育中所起作用的知识。这种蛋白质在大脑发育中的作用与其携带脂肪酸的能力密切相关。因此，白蛋白通过星形胶质细胞刺激油酸合成，这些油酸来自大脑发育期间可用的主要代谢底物。星形胶质细胞通过受体介导的内吞作用将白蛋白内化到囊泡样结构中，随后进行转胞吞作用，包括穿过内质网（ER）。内质网中白蛋白的存在会激活固醇调节元件结合蛋白-1（SREBP-1）并增加硬脂酰辅酶A 9-去饱和酶（SCD）mRNA，这是油酸合成中的关键酶。星形胶质细胞释放的油酸被神经元用于合成磷脂，并特异性地整合到生长锥中。此外，油酸促进轴突生长、神经元聚集以及轴突生长相关蛋白GAP-43的表达。所有这些观察结果都表明了神经元的分化。油酸对GAP-43合成的影响是由蛋白激酶C的激活引起的。在与星形胶质细胞共培养的神经元中，白蛋白的存在会显著增加GAP-43的表达，这表明神经元分化是由星形胶质细胞原位合成和释放的油酸所引起的。总之，在大脑发育过程中，白蛋白的存在可能通过触发星形胶质细胞合成和释放油酸来发挥重要作用，从而诱导神经元分化。
