Impaired Endoplasmic Reticulum Stress Response in B-Lymphoblasts From Patients With Bipolar-I Disorder

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• 作者：Jonathan So ; Jerry J. Warsh ; Peter P. Li
• 刊名：Biological Psychiatry
• 出版年：2007
• 出版时间：15 July 2007
• 年：2007
• 卷：62
• 期：2
• 页码：141-147
• 全文大小：374 K

文摘

Backgroud

Aberrant intracellular calcium (Ca²⁺) signaling in patients with bipolar-I disorder (BD-I) suggests disturbed endoplasmic reticulum (ER) function in BD. We examined whether the ER stress response is altered in BD-I patients and the relationship to basal intracellular Ca²⁺ levels ([Ca²⁺]_B), in B lymphoblasts (BLCLs) from BD-I patients.

Methods

Endoplasmic reticulum stress-induced X-box binding protein 1 (XBP1), C/EBP homologous protein (CHOP), and GRP78 expression in BLCLs from BD-I subjects stratified on elevated or normal [Ca²⁺]_B and control subjects were determined by real-time quantitative reverse transcription polymerase chain reaction. The XBP1 212;116C/G polymorphism, which impairs the XBP1 loop in the ER stress response, were genotyped with a TaqMan-based assay.

Results

Compared with control subjects, thapsigargin- and tunicamycin-induced increases in XBP1 and CHOP but not GRP78 messenger RNA levels were significantly lower in BD-I patients. However, induction of these genes did not differ significantly in the two BD-I subgroups stratified on [Ca²⁺]_B. Furthermore, the attenuated XBP1 induction cannot be explained solely by differences of XBP1 212;116C/G genotype frequency.

Conclusions

Our findings suggest that the ER stress response is impaired in BD-I patients but irrespective of altered intracellular Ca²⁺ homeostasis as reflected in elevated [Ca²⁺]_B. Moreover, an effect of XBP1 212;116C/G polymorphism could not account for the attenuated XBP1 induction in bipolar-I disorder observed in this study.