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Abstract
Seipin is a widely expressed protein but with highest levels found in the brain and testes. Seipin function is not yet completely understood, therefore the aim of this study was to evaluate the expression of BSCL2 transcripts in the central nervous system (CNS) of humans and investigate the effect of their overexpression on a neuron model and their relationship with oxidative stress protection, as well as shed light on the pathogenic mechanisms of Celia’s Encephalopathy. We analyzed the expression of BSCL2 transcripts using real-time RT–PCR in samples across the brain regions of subjects who underwent necropsy and from a case with Celia’s Encephalopathy. The transcript encoding the long seipin isoform (BSCL2-203, 462 aa) is expressed primarily in the brain and its expression is inversely correlated with age in the temporal lobe, amygdala, and hypothalamus. Strong positive correlations were found between BSCL2 expression and some genes encoding protective enzymes against oxidative stress including SOD1 and SOD2, as well as peroxisome proliferator-activated receptor gamma (PPARG) in the amygdala. These results were experimentally corroborated by overexpressing BSCL2 transcripts in SH-SY5Y cells with lentiviral transduction and assessing their effects on neuron differentiated cells. Confocal microscopy studies showed that both seipin and PEX16 are closely expressed in the hypothalami of healthy human brains, and PEX16 was absent in the same region of the PELD case. We hypothesize that seipin has specific CNS functions and may play a role in peroxisome biogenesis.
Highlights
The BSCL2 gene encodes seipin, a resident endoplasmic reticulum (ER) protein with two transmembrane domains, a luminal loop, and two amino and carboxy-terminal tails in the cytoplasm.The BSCL2 gene principally encodes three seipin isoforms under natural conditions, 462 (BSCL2-203, ENST00000360796.9; CCDS44627), 398 (BSCL2-205/207/ 210, ENST00000403550.5; ENST00000407022.7; ENST00000421906.5; CCDS8031), and 287 (BSCL2201, ENST00000278893.11; CCDS55769) amino acids long, respectively
This study describes the differential expression of the BSCL2 in the human brain and other tissues, and identifies BSCL2-203 as the major transcript in the central nervous system (CNS)
BSCL2-205/207/210 is primarily expressed in the extraneural tissues, and the transcript responsible for the Celia-seipin (BSCL2-201) is expressed very little but mainly in the caudate, one of the nuclei affected earliest in Celia’s Encephalopathy (Araujo-Vilar et al, 2018)
Summary
The BSCL2 gene encodes seipin, a resident endoplasmic reticulum (ER) protein with two transmembrane domains, a luminal loop, and two amino and carboxy-terminal tails in the cytoplasm. The BSCL2 gene principally encodes three seipin isoforms under natural conditions, 462 (BSCL2-203, ENST00000360796.9; CCDS44627), 398 (BSCL2-205/207/ 210, ENST00000403550.5; ENST00000407022.7; ENST00000421906.5; CCDS8031), and 287 (BSCL2201, ENST00000278893.11; CCDS55769) amino acids long, respectively. BSCL2-210/207/205 was the first transcript to be described (Magre et al, 2001), and BSCL2-203 is the same as BSCL2-210/207/205 except for an N-terminal extension of 64 amino acids encoded by exon 1 and part of exon 2.
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