An Allel-Specific Abnormal Transcript of the Heat Shock Protein 70 Gene in Patients with Major Depression

Shimizu, Shoichi; Nomura, Kazuhiro; Ujihara, Makoto; Sakamoto, Kaoru; Shibata, Hiroo; Suzuki, Takashiro; Demura, Hiroshi

doi:10.1006/bbrc.1996.0305

Cited by 30 publications

(13 citation statements)

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“…33 In addition, some studies show that alterations in HSP70 or 90 are accompanied by mood disorders. 62,63 However, we did not find different HSP70 or 90 expressions in the PVN in depressed patients and the data therefore do not support a central role for these HSP molecules in depression.…”

Section: Hspcontrasting

confidence: 83%

Gene expression analysis in the human hypothalamus in depression by laser microdissection and real-time PCR: the presence of multiple receptor imbalances

et al. 2008

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Hyperactivity of corticotropin-releasing factor (CRF) neurons in the paraventricular nucleus (PVN) of the hypothalamus is a prominent feature in depression and may be important in the etiology of this disease. The activity of the CRF neurons in the stress response is modulated by a number of factors that stimulate or inhibit CRF expression, including (1) corticosteroid receptors and their chaperones, heat shock proteins 70 and 90, (2) sex hormone receptors, (3) CRF receptors 1 (CRFR1) and 2, (4) cytokines interleukin 1-b and tumor necrosis factor-a, (5) neuropeptides and receptors, vasopressin (AVP), AVP receptor 1a (AVPR1A) and oxytocin and (6) transcription factor cAMP-response element-binding protein. We hypothesized that, in depression, the transcript levels of those genes that are involved in the activation of the hypothalamo-pituitary-adrenal (HPA) axis are upregulated, whereas the transcript levels of the genes involved in the inhibition of the HPA axis are downregulated. We performed laser microdissection and real-time PCR in the PVN and as a control in the supraoptic nucleus. Snap-frozen post-mortem hypothalami of seven depressed and seven matched controls were used. We found significantly increased CRF mRNA levels in the PVN of the depressed patients. This was accompanied by a significantly increased expression of four genes that are involved in the activation of CRF neurons, that is, CRFR1, estrogen receptor-a, AVPR1A and mineralocorticoid receptor, while the expression of the androgen receptor mRNA involved in the inhibition of CRF neurons was decreased significantly. These findings raise the possibility that a disturbed balance in the production of receptors may contribute to the activation of the HPA axis in depression.

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Section: Hspcontrasting

confidence: 83%

Gene expression analysis in the human hypothalamus in depression by laser microdissection and real-time PCR: the presence of multiple receptor imbalances

et al. 2008

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“…Differential HSP expression in human diseases is also supported by several studies (Deguchi and Kishimoto 1990;Dhillon et al 1993;Vignola et al 1995;Shimizu et al 1996). To our knowledge, there are no reports concerning the possible candidate gene HSP70 in PD.…”

Section: Introductionmentioning

confidence: 54%

Analysis of heat-shock protein�70 gene polymorphisms and the risk of Parkinson?s disease

et al. 2004

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Parkinson's disease (PD) involves several genetic and environmental components. Heat-shock protein 70, a chaperone that is up-regulated in stress responses and that refolds protein, may be involved in the pathogenesis of PD. We have investigated the association of polymorphisms -110 A/C, +190 G/C, +1267 A/G, +2074 G/C, and +2437 G/C in the 5' and coding regions of the HSP70-1, HSP70-2, and HSP70-hom genes with the risk of PD by screening DNA samples from 274 PD patients and 183 controls in assays based on the polymerase chain reaction. There was no statistically significant difference in genotype distribution between patients and controls for the three coding-region polymorphisms in HSP70-2 and HSP70-hom. However, for HSP70-1, the overall genotype distribution was significantly different at the -110 site (P=0.004) and tended to be different at the +190 site (P=0.012) between patients and controls. The frequencies of the -110 CC and +190 CC genotypes were significantly higher in PD patients than in controls (P=0.001 and 0.006, respectively). Both -110 CC (odds ratio: 2.91; 95% CI: 1.51-5.96; P=0.002) and +190 CC (odds ratio: 3.59; 95% CI: 1.53-9.88; P=0.006) genotypes were significantly associated with PD. Reporter constructs containing the -110 A allele cloned into a luciferase reporter plasmid drove marginally higher transcriptional activity of HSP70-1 compared with the -110 C allele in both control and heat-shocked IMR32 and 293 cells. Therefore, -110 A/C may be a functional polymorphism in the 5' promoter region of HSP70-1 and may affect susceptibility to PD.

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“…Furthermore, one of the heat shock genes on chromosome 6 may be involved. Only in patients with depression, a shorter mRNA of the HSPAlA locus was found, which was not translated into the corresponding protein (Shimizu et al, 1996). Since there is, so far, no independent evidence for the association of either PREP or HSPAlA with affective disorder, we have to await the outcome of additional studies.…”

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confidence: 98%

Biology of Chromosome 6

Ziegler

1997

DNA Sequence

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The major histocompatibility (HLA) complex on the short arm of human chromosome 6 has attracted many scientists over the last three decades. It is the purpose of this brief review to point out that the remaining large regions of chromosome 6 contain genes involved in several interesting biological phenomena as well. Focus will be particularly on genes affecting behavioural features and sensory perception. The likely involvement of HLA and closely linked olfactory receptor loci in mate selection and their possible role in favouring heterozygosity among the offspring will also be discussed.

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An Allel-Specific Abnormal Transcript of the Heat Shock Protein 70 Gene in Patients with Major Depression

Cited by 30 publications

References 0 publications

Gene expression analysis in the human hypothalamus in depression by laser microdissection and real-time PCR: the presence of multiple receptor imbalances

Gene expression analysis in the human hypothalamus in depression by laser microdissection and real-time PCR: the presence of multiple receptor imbalances

Analysis of heat-shock protein�70 gene polymorphisms and the risk of Parkinson?s disease

Biology of Chromosome 6

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