Promoter polymorphisms modulating HSPA5 expression may increase susceptibility to Taiwanese Alzheimer’s disease

Hsu, Wen‐Chuin; Wang, H. K.; Lee, L. C.; Fung, Hon Chung; Jian, Lin; Hsu, Hai Pei; Wu, Yonggui; Ro, Long Sun; Hu, Fen Ju; Chang, Yung-Ta; Lee-Chen, Guey Jen; Chen, C. M.

doi:10.1007/s00702-008-0117-5

Cited by 28 publications

(33 citation statements)

References 23 publications

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“…The genotype-dependent increase of the GRP78 protein may inhibit the b cell apoptosis and maintain the glucose homeostasis (as the data were shown in our study). The findings are supported by the studies that the high activity of -415AA/-180GG genotypes of GRP78 alleviated the ER stress in lymphoblastoid cells treated with thapsigargin (Laybutt et al, 2007;Hsu et al, 2008). Moreover, the findings have the resonance with a study showing that GRP78 partially rescued high glucose-induced suppression of proinsulin levels and improved glucose-stimulated insulin secretion (GRP78 is essential for insulin biosynthesis, and enhancing the chaperone capacity can improve b cell function in the presence of prolonged hyperglycemia) (Zhang et al, 2009).…”

Section: Discussionsupporting

confidence: 59%

“…So far, most studies on population-dependent variations in the allele frequency of GRP78 polymorphisms have been performed in Asia. Among Taiwanese healthy controls, similar -415A ( -180G) and -370T allele frequencies were observed, ranging from 30.6% to 31.9% and 45.8% to 46.8%, respectively Hsu et al, 2008;Lee et al, 2008). These allele frequencies were lower than those frequencies ( -415A [ -180G]: 34.0% and -370T: 59.8%) in Japanese healthy controls (Sakurai et al, 2007).…”

Section: Discussionmentioning

confidence: 95%

“…Kakiuchi et al (2005) suggested that promoter polymorphisms of GRP78 may affect the interindividual variability of the ER stress response and may confer a genetic risk factor for bipolar disorder. Hsu et al (2008) reported that GRP78 may increase susceptibility to Alzheimer's disease among Taiwanese. Zhu et al (2011) demonstrated that the polymorphisms of GRP78 constituted a risk factor for the development of advanced liver cirrhosis in one study, and was associated with reduced survival and a higher prevalence of early relapses in advanced patients with nonsmall cell lung cancer in another study.…”

Section: Introductionmentioning

confidence: 99%

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Association Between Promoter Polymorphisms of the GRP78 Gene and Risk of Type 2 Diabetes in a Chinese Han Population

Liu

Li²,

Li³

et al. 2013

DNA and Cell Biology

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There are large amounts of unfolding or misfolding protein accumulation in the endoplasmic reticulum in patients with type 2 diabetes (T2D), which in turn induces the expression of the glucose-regulated protein 78 (GRP78) that plays a key role in influencing insulin secretion and maintaining glucose homeostasis in pancreatic beta cells. The aim in the study is to analyze the potential association between single-nucleotide polymorphisms (SNPs) of GRP78 and the risk of T2D. To assess the association between GRP78 polymorphisms and T2D, a casecontrol study was conducted among 1058 consecutive unrelated subjects. Of the 1058 subjects, 523 of them were diagnosed with T2D and 535 of them were healthy controls. Four SNPs with R 2 > 0.8 and the minor allele frequency > 0.05 (rs391957, rs17840761, rs17840762, and rs11355458) in the GRP78 gene promoter were analyzed. Overall, no associations of GRP78 polymorphisms with T2D were observed in genotypic analyses. In addition, haplotypes combining those SNPs in the promoter in high linkage disequilibrium were also not associated with a T2D risk. However, the levels of fasting plasma glucose and HbA1c in patients with the -415AA/-180GG genotype were significantly lower than those of the patients with -415GG/-180deldel and -415AG/-180Gdel genotypes, and the level of fasting insulin in patients with the -415AA/-180GG genotype was significantly lower than that of the patients with -415GG/ -180deldel. The study does not support a role for promoter polymorphisms of GRP78 in T2D in a Chinese Han population, but it does provide a clue for association between low levels of fasting plasma glucose, HbA1c and fasting insulin, and the -415AA/-180GG model.

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Section: Discussionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

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Association Between Promoter Polymorphisms of the GRP78 Gene and Risk of Type 2 Diabetes in a Chinese Han Population

Liu

Li²,

Li³

et al. 2013

DNA and Cell Biology

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“…Overexpression of Grp78 together with APP in cells has been shown to decrease A␤ production, perhaps due to inhibition of APP maturation (25,48). Furthermore, a polymorphism allele of the human Grp78 promoter, which results in greater responses to ER stress, was reported to decrease the risk of AD (49). We, for the first time, validated this interaction in an endogenous model in vivo and identified the APP N-terminal domain as its interaction site.…”

Section: Discussionmentioning

confidence: 56%

Amyloid Precursor Protein Revisited

Guo

Gaddam

et al. 2012

Journal of Biological Chemistry

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“…The ER chaperone protein GRP78 (HSPA5) is involved in the folding and assembly of proteins in the ER (86). Its synthesis can be stimulated by stress conditions that perturb ER function and calcium homeostasis (87).…”

Section: Exploring Novel CC Protein Interaction Partners Using Amentioning

confidence: 99%

Structural and Functional Analysis of Novel Human Cytochrome c Targets in Apoptosis

Martínez-Fábregas

Dı́az-Moreno

González‐Arzola

et al. 2014

Molecular & Cellular Proteomics

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Since the first description of apoptosis four decades ago, great efforts have been made to elucidate, both in vivo and in vitro, the molecular mechanisms involved in its regulation. Although the role of cytochrome c during apoptosis is well established, relatively little is known about its participation in signaling pathways in vivo due to its essential role during respiration. To obtain a better understanding of the role of cytochrome c in the onset of apoptosis, we used a proteomic approach based on affinity chromatography with cytochrome c as bait in this study. In this approach, novel cytochrome c interaction partners were identified whose in vivo interaction and cellular localization were facilitated through bimolecular fluorescence complementation. Modeling of the complex interface between cytochrome c and its counterparts indicated the involvement of the surface surrounding the heme crevice of cytochrome c, in agreement with the vast majority of known redox adducts of cytochrome c. However, in contrast to the high turnover rate of the mitochondrial cytochrome c redox adducts, those occurring under apoptosis led to the formation of stable nucleo-cytoplasmic ensembles, as inferred mainly from surface plasmon resonance and nuclear magnetic resonance measurements, which permitted us to corroborate the formation of such complexes in vitro. The results obtained suggest that human cytochrome c interacts with pro-survival, anti-apoptotic proteins following its release into the cytoplasm. Thus, cytochrome c may interfere with cell survival pathways and unlock apoptosis in order to prevent the spatial and temporal coexistence of antagonist signals. Molecular & Cellular

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Promoter polymorphisms modulating HSPA5 expression may increase susceptibility to Taiwanese Alzheimer’s disease

Cited by 28 publications

References 23 publications

Association Between Promoter Polymorphisms of the GRP78 Gene and Risk of Type 2 Diabetes in a Chinese Han Population

Association Between Promoter Polymorphisms of the GRP78 Gene and Risk of Type 2 Diabetes in a Chinese Han Population

Amyloid Precursor Protein Revisited

Structural and Functional Analysis of Novel Human Cytochrome c Targets in Apoptosis

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