Transcytosis of albumin in astrocytes activates the sterol regulatory element-binding protein-1, which promotes the synthesis of the neurotrophic factor oleic acid.

Arantxa Tabernero,Begoña Granda,José M Medina,Eva M Lavado,Ana Velasco

doi:10.1074/jbc.m108760200

Arantxa Tabernero, Begoña Granda + Show 3 more

Open Access

https://doi.org/10.1074/jbc.m108760200

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Abstract

We have recently reported that albumin, a serum protein present in the developing brain, stimulates the synthesis of oleic acid by astrocytes, which promotes neuronal differentiation. In this work, we gain insight into the mechanism by which albumin induces the synthesis of this neurotrophic factor. Our results show that astrocytes internalize albumin in vesicle-like structures by receptor-mediated endocytosis. Albumin uptake was followed by transcytosis, including passage through the endoplasmic reticulum, which was required to induce the synthesis of oleic acid. Oleic acid synthesis is feedback-regulated by the sterol regulatory element-binding protein-1, which induces the transcription of stearoyl-CoA 9-desaturase, the key rate-limiting enzyme for oleic acid synthesis. In our research, the presence of albumin activated the sterol regulatory element-binding protein-1 and increased stearoyl-CoA 9-desaturase mRNA. Moreover, when the activity of sterol regulatory element-binding protein-1 was inhibited by overexpression of a truncated form of this protein, albumin did not affect stearoyl-CoA 9-desaturase mRNA, indicating that the effect of albumin is mediated by this transcription factor. The effect of albumin was abolished when traffic to the endoplasmic reticulum was prevented or when albumin was accompanied with oleic acid. In conclusion, our results suggest that the transcytosis of albumin includes passage through the endoplasmic reticulum, where oleic acid is sequestrated, initiating the signal cascade leading to an increase in its own synthesis.

Highlights

Astrocytes, the main glial cell population in the central nervous system, play a major role in supporting the development of neurons
Our results showed that after 5 min of treatment with trypsin or Pronase, astrocytes lost their ability to take up albumin (Fig. 1E)
To investigate whether the effect of albumin on sterol regulatory element-binding protein-1 (SREBP-1) might be associated with changes in the mRNA synthesis of stearoyl-CoA 9-desaturase (SCD), an enzyme located in the endoplasmic reticulum (ER) that catalyzes the formation of the ⌬9-cis-double bond of oleic acid, Northern blot analysis was performed with RNA extracts from astrocytes under the same experimental conditions as those used to investigate

Summary

Introduction

Astrocytes, the main glial cell population in the central nervous system, play a major role in supporting the development of neurons. To gain insight into the mechanism by which albumin is taken up by astrocytes, cells were exposed to FITC-BSA in the absence or in the presence of PAO, an inhibitor of receptor-mediated endocytosis (28).

Results

Conclusion