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Aberrant endoplasmic reticulum stress response in lymphoblastoid cells from patients with bipolar disorder
- Source :
- The International Journal of Neuropsychopharmacology. 12:33
- Publication Year :
- 2008
- Publisher :
- Oxford University Press (OUP), 2008.
-
Abstract
- Impaired endoplasmic reticulum (ER) stress response has been suggested as a possible pathophysiological mechanism of bipolar disorder (BD). The expression of ER stress-related genes, spliced form or unspliced form of XBP1, GRP78 (HSPA5), GRP94 (HSP90B1), CHOP (DDIT3), and calreticulin (CALR), were examined in lymphoblastoid cells derived from 59 patients with BD and 59 age- and sex-matched control subjects. Basal mRNA levels and induction by 4 h or 12 h of treatment with two ER stressors, thapsigargin or tunicamycin, were examined using real-time quantitative reverse transcription-polymerase chain reaction. Induction of the spliced form of XBP1 as well as total XBP1 by thapsigargin was significantly attenuated in patients with BD. Induction of GRP94 by thapsigargin was also decreased in the BD group. A haplotype of GRP94, protective against BD, exhibited significantly higher GRP94 expression upon ER stress. This report confirms and extends earlier observations of impaired ER stress response in larger samples of lymphoblastoid cell lines derived from BD patients. Altered ER stress response may play a role in the pathophysiology of BD by altering neural development and plasticity.
- Subjects :
- Adult
Male
Protein Folding
medicine.medical_specialty
Bipolar Disorder
XBP1
Thapsigargin
Genotype
CHOP
Endoplasmic Reticulum
chemistry.chemical_compound
Stress, Physiological
Internal medicine
medicine
Humans
HSP70 Heat-Shock Proteins
Pharmacology (medical)
Lymphocytes
Enzyme Inhibitors
Endoplasmic Reticulum Chaperone BiP
Cells, Cultured
Psychiatric Status Rating Scales
Pharmacology
biology
Reverse Transcriptase Polymerase Chain Reaction
Tunicamycin
Lymphoblast
Endoplasmic reticulum
Membrane Proteins
Middle Aged
Psychiatry and Mental health
Endocrinology
Gene Expression Regulation
chemistry
Unfolded protein response
biology.protein
RNA
Female
Calreticulin
Subjects
Details
- ISSN :
- 14695111 and 14611457
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- The International Journal of Neuropsychopharmacology
- Accession number :
- edsair.doi.dedup.....c55251cdf2e65fbb854fc9c9db5595e3