Lack of association between the GRP78 polymorphisms in the promoter and 3' UTR and susceptibility to chronic HBV infection in a Chinese Han population.

BACKGROUND: Hepatitis B virus (HBV) infection causes large amount of unfolding or false-folding protein accumulation in the endoplasmic reticulum (ER), which in turn induces the expression of glucose-regulated protein 78 (GRP78). The aim in the present study was to analyse the potential association between GRP78 single-nucleotide polymorphisms (SNPs) and the risk of HBV infection. METHODS: The associations between seven common GRP78 polymorphisms in the promoter (rs391957, rs17840762, rs17840761, rs11355458) and in the 3' untranslated region (UTR) (rs16927997, rs1140763, rs12009) and possible risk of chronic HBV infection were assessed in a case-control study. 496 cases and 539 individually matched healthy controls were genotyped. RESULTS: Overall, no associations were observed in genotypic analyses. In addition, haplotypes and diplotypes combining those SNPs in the promoter or in the 3' UTR in high linkage disequilibrium (LD) were also not associated with HBV risk. CONCLUSION: These observations do not support a role for GRP78 polymorphisms in HBV infection in a predominantly Chinese Han population.

Single nucleotide polymorphism of rs430397 in the fifth intron of GRP78 gene and clinical relevance of primary hepatocellular carcinoma in Han Chinese: risk and prognosis.

Large number of data showed that allele variants in certain genes are markers for hepatocellular carcinoma (HCC). GRP78 is a stress-associated protein which is a central regulator of endoplasmic reticulum homeostasis due to its multiple functional roles in the folding, maturation and transport of proteins. A case-control study was conducted on 576 HCC patients, and 539 age- and gender-matched healthy subjects to examine whether rs430397 polymorphism in the fifth intron of GRP78 gene is associated with the development and prognosis of HCC. Polymorphism in rs430397 was analyzed by resequencing and TaqMan real-time PCR. Allele A, genotype AA and combined genotypes (AG+AA) displayed significantly increased risk for HCC (OR = 1.48, 95%CI = 1.07-1.79, p = 0.010; OR = 2.25, 95%CI = 1.08-3.38, p = 0.019; and OR = 1.50, 95%CI = 1.09-1.85, p = 0.012, respectively). Genotypes AA and AG were mainly associated with HBV-related HCC (85.8%; p < 0.00001 versus HBV noncarriers with HCC) and cirrhosis-related HCC (90%; p = 0.011 versus noncirrhosis HCC). Patients carrying the AA genotype had a shorter survival time (median 23.0 months in all cases; median 21.0 months in the cases carrying HBsAg). Like HBV and cirrhosis, the rs430397 is an independent prognostic factor influencing the survival of HCC. In conclusion, allele A and genotypes AA and AG of rs430397 may represent high risk and poor prognosis for HCC.

Postnatal development of nestin positive neurons in rat basal forebrain: different onset and topography with choline acetyltransferase and parvalbumin expression.

Our previous studies identified a sub-population of cholinergic neurons which express nestin in the rostral part of the basal forebrain (BF) in normal adult rats. In the present study, the postnatal developmental patterns of nestin, choline acetyl transferase (ChAT) and parvalbumin (PV) positive neurons were explored by means of immunohistochemistry combined with immunofluorescence double label methods. Compared with early onset of ChAT expression (from P1) and delayed onset of PV expression (from P16), nestin positive activity was detected in the BF from P9 and co-expressed by parts of the ChAT positive neurons within the same region during the whole postnatal development process. However, ChAT and PV were not coexpressed by the neurons within the medial septum-diagonal band of Broca (MS-DBB) of BF. These results might imply a composite of separate development patterns displayed by different subpopulations of cholinergic neurons (nestin positive cholinergic neurons and nestin negative cholinergic neurons) within this region. Moreover, the topographic distribution of nestin, ChAT and PV positive neurons also showed different characteristics. In summary, our present study revealed a remarkable timing and topographic difference on the postnatal development of the nestin expression within the MS-DBB of BF compared with ChAT and PV expression. It is further suggested that nestin is re-expressed by cholinergic neurons in the BF after differentiation but not persisted from neuronal precursor cells.

Heme oxygenase-1 and gut ischemia/reperfusion injury: A short review.

Ischemia/reperfusion (I/R) injury of the gut is a significant problem in a variety of clinical settings and is associated with a high morbidity and mortality. Although the mechanisms involved in the pathogenesis of gut I/R injury have not been fully elucidated, it is generally believed that oxidative stress with subsequent inflammatory injury plays an important role. Heme oxygenase (HO) is the rate-limiting enzyme in the catabolism of heme, followed by production of CO, biliverdin, and free iron. The HO system is believed to confer cytoprotection by inhibiting inflammation, oxidation, and apoptosis, and maintaining microcirculation. HO-1, an inducible form of HO, serves a vital metabolic function as the rate-limiting step in the heme degradation pathway, and affords protection in models of intestinal I/R injury. HO-1 system is an important player in intestinal I/R injury condition, and may offer new targets for the management of this condition.

Heme oxygenase-1 system and gastrointestinal inflammation: a short review.

Heme oxygenase-1 (HO-1) system catalyzes heme to biologically active products: carbon monoxide, biliverdin/bilirubin and free iron. It is involved in maintaining cellular homeostasis and many physiological and pathophysiological processes. A growing body of evidence indicates that HO-1 activation may play an important protective role in acute and chronic inflammation of gastrointestinal tract. This review focuses on the current understanding of the physiological significance of HO-1 induction and its possible roles in the gastrointestinal inflammation studied to date. The ability to upregulate HO-1 by pharmacological means or using gene therapy may offer therapeutic strategies for gastrointestinal inflammation in the future.

Heme oxygenase-1 system and gastrointestinal tumors.

Heme oxygenase-1 (HO-1) system catabolizes heme into three products: carbon monoxide, biliverdin/bilirubin and free iron. It is involved in many physiological and pathophysiological processes. A great deal of data has demonstrated the roles of HO-1 in the formation, growth and metastasis of tumors. The interest in this system by investigators involved in gastrointestinal tumors is fairly recent, and few papers on HO-1 have touched upon this subject. This review focuses on the current understanding of the physiological significance of HO-1 induction and its possible roles in the gastrointestinal tumors studied to date. The implications for possible therapeutic manipulation of HO-1 in gastrointestinal tumors are also discussed.

Chemical identification of nestin-immunoreactive neurons in the rat basal forebrain: a re-examination.

This study explores recently identified neurons that express the protein nestin in the medial septum-diagonal band of Broca (MS-DBB) of adult rats and humans. These nestin positive neurons from MS-DBB are known to project to the hippocampus and frontal cortex of the brain. However, their chemical identification has not been fully elucidated. In this study, we further investigated the chemical identity of the nestin-immunoreactive (ir) neurons in rats using double immunofluorescence labeling and single cell reverse transcription polymerase chain reaction (RT-PCR) techniques. The results of double labeling showed that all nestin-ir neurons exhibited choline acetyltransferase (ChAT) immunoreactivity in the MS-DBB of the basal forebrain. Conversely, only about 43% of the ChAT-ir neurons showed nestin immunoreactivity. In addition, a vast majority of the nestin-ir neurons (95%) were nerve growth factor receptor (NGFR) positive. The nestin-ir neurons were highly distributed in the rostral and intermediated regions of the MS-DBB. Single cell RT-PCR results showed that 90% of the nestin mRNA expressed neurons displayed ChAT mRNA expression as well, but neither the mRNA of the proteins glutamic acid decarboxylases 67 (GAD67) nor vesicular glutamate transporters (VGLUTs). These results provide the first evidence that nestin-ir neurons in the basal forebrain are a subpopulation of the classic cholinergic neurons. With high NGFR proteins activated in the nestin-ir neurons, we propose that the presence of nestin in the cholinergic neurons might be related to the survival and plasticity of the cholinergic neurons.

A new polymorphism in the GRP78 is not associated with HBV invasion.

AIM: To examine the association between -86 bp (T > A) in the glucose-regulated protein 78 gene (GRP78) and hepatitis B virus (HBV) invasion. METHODS: DNA was genotyped for the single-nucleotide polymorphism by polymerase chain reaction followed by sequencing in a sample of 382 unrelated HBV carriers and a total of 350 sex- and age-matched healthy controls. Serological markers for HBV infection were determined by enzyme-linked immunosorbent assay kits or clinical chemistry testing. RESULTS: The distributions of allelotype and genotype in cases were not significantly different from those in controls. In addition, our findings suggested that neither alanine aminotransferase/hepatitis B e antigen nor HBV-DNA were associated with the allele/genotype variation in HBV infected individuals. CONCLUSION: -86 bp T > A polymorphism in GRP78 gene is not related to the clinical risk and acute exacerbation of HBV invasion.