Functional Polymorphisms of the Lss and Fdft1 Genes in Laboratory Rats

Mori, Masayuki; Sawashita, Jinko; Higuchi, Kenichi

doi:10.1538/expanim.56.93

Cited by 6 publications

(5 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…23 The levels of LSS did not markedly change on MPP+ addition (Figure 4a, fourth panel from top). Interestingly, however, we observed a different localization pattern of LSS in MPP+-treated dopaminergic neurons.…”

Section: Resultsmentioning

confidence: 91%

Lanosterol induces mitochondrial uncoupling and protects dopaminergic neurons from cell death in a model for Parkinson's disease

et al. 2011

View full text Add to dashboard Cite

Parkinson's disease (PD) is a neurodegenerative disorder marked by the selective degeneration of dopaminergic neurons in the nigrostriatal pathway. Several lines of evidence indicate that mitochondrial dysfunction contributes to its etiology. Other studies have suggested that alterations in sterol homeostasis correlate with increased risk for PD. Whether these observations are functionally related is, however, unknown. In this study, we used a toxin-induced mouse model of PD and measured levels of nine sterol intermediates. We found that lanosterol is significantly (∼50%) and specifically reduced in the nigrostriatal regions of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice, indicative of altered lanosterol metabolism during PD pathogenesis. Remarkably, exogenous addition of lanosterol rescued dopaminergic neurons from 1-methyl-4-phenylpyridinium (MPP+)-induced cell death in culture. Furthermore, we observed a marked redistribution of lanosterol synthase from the endoplasmic reticulum to mitochondria in dopaminergic neurons exposed to MPP+, suggesting that lanosterol might exert its survival effect by regulating mitochondrial function. Consistent with this model, we find that lanosterol induces mild depolarization of mitochondria and promotes autophagy. Collectively, our results highlight a novel sterol-based neuroprotective mechanism with direct relevance to PD.

show abstract

Section: Resultsmentioning

confidence: 91%

Lanosterol induces mitochondrial uncoupling and protects dopaminergic neurons from cell death in a model for Parkinson's disease

et al. 2011

View full text Add to dashboard Cite

show abstract

“…We should also mention some other biomarkers that could be interesting for further studies, including imaging purposes, like TSPO/PBR (translocator protein (18kDa)) also known as Mitochondrial Benzodiazepine Receptor (peripheral), thus supporting its current role as a putative imaging biomarker for AD [448], [449], [450], [451], [452], [453], [454], [455], C1S (complement component 1, s subcomponent) [456], [457], [458], [459], [460], [461], FDFT1 (the squalene synthase gene), which is critical for cholesterol synthesis [462], [463], BMP4 [92], [96], [464], [465], CD68 (as marker of enhanced lysosomal activity) [450], [466], [467], [468], [469], [470], [471], [472], SERTAD2/TRIP-Br2 [473], [474], [475], LTF (Lactotransferrin) [476], [477], [478], FTL (ferritin, light polypeptide; Ferritin light chain) [479], [480], [481], [482], MTF1 (Metal-regulatory transcription factor 1) [483], [484], [485], GSTA3 (Glutathione S-transferase A3), GSTM4 (Glutathione S-transferase M4), MT1L (Metallothionein 1L (gene/pseudogene) [486] (a human-specific truncated protein which may have changed its function or suppressed it [487]), MT1H (Metallothionein 1H) [488], MT1F (Metallothionein 1F) [488], [489] (Figure 16). These last three upregulated genes need to be put in concert with other reports on methallothioneins in AD brains [490], [491], [492].…”

Section: Resultsmentioning

confidence: 91%

Uncovering Molecular Biomarkers That Correlate Cognitive Decline with the Changes of Hippocampus' Gene Expression Profiles in Alzheimer's Disease

et al. 2010

View full text Add to dashboard Cite

BackgroundAlzheimer's disease (AD) is characterized by a neurodegenerative progression that alters cognition. On a phenotypical level, cognition is evaluated by means of the MiniMental State Examination (MMSE) and the post-morten examination of Neurofibrillary Tangle count (NFT) helps to confirm an AD diagnostic. The MMSE evaluates different aspects of cognition including orientation, short-term memory (retention and recall), attention and language. As there is a normal cognitive decline with aging, and death is the final state on which NFT can be counted, the identification of brain gene expression biomarkers from these phenotypical measures has been elusive.Methodology/Principal FindingsWe have reanalysed a microarray dataset contributed in 2004 by Blalock et al. of 31 samples corresponding to hippocampus gene expression from 22 AD subjects of varying degree of severity and 9 controls. Instead of only relying on correlations of gene expression with the associated MMSE and NFT measures, and by using modern bioinformatics methods based on information theory and combinatorial optimization, we uncovered a 1,372-probe gene expression signature that presents a high-consensus with established markers of progression in AD. The signature reveals alterations in calcium, insulin, phosphatidylinositol and wnt-signalling. Among the most correlated gene probes with AD severity we found those linked to synaptic function, neurofilament bundle assembly and neuronal plasticity.Conclusions/SignificanceA transcription factors analysis of 1,372-probe signature reveals significant associations with the EGR/KROX family of proteins, MAZ, and E2F1. The gene homologous of EGR1, zif268, Egr-1 or Zenk, together with other members of the EGR family, are consolidating a key role in the neuronal plasticity in the brain. These results indicate a degree of commonality between putative genes involved in AD and prion-induced neurodegenerative processes that warrants further investigation.

show abstract

“…The FDFT1 gene functions as a key regulator in the cholesterol biosynthesis pathway. 55 FDFT1 directs sterol biosynthesis to a branch resulting in the exclusive synthesis of cholesterol. 56 This was inconsistent with the result of this study that FDFT1 was enriched in the cholesterol biosynthesis process.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis of hepatitis C virus genotype 2a-induced human hepatocellular carcinoma in Huh7 cells

Xu¹,

Wu²,

Chen³

et al. 2016

OTT

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is a liver cancer that could be induced by hepatitis C virus genotype 2a Japanese fulminant hepatitis-1 (JFH-1) strain. The aim of this study was to investigate the molecular mechanisms of HCC. The microarray data GSE20948 includes 14 JFH-1- and 14 mock (equal volume of medium [control])-infected Huh7 samples. The data were downloaded from the Gene Expression Omnibus. After data processing, soft cluster analyses were performed to identify co-regulated genes with similar temporal expression patterns. Functional and pathway enrichment analyses, as well as functional annotation analysis, were performed. Subsequently, combined networks of protein–protein interaction network, microRNA regulatory network, and transcriptional regulatory network were constructed. Hub nodes, modules, and five clusters of co-regulated genes were also identified. In total, 173 up and 207 down co-regulated genes were separately identified in JFH-1-infected Huh7 cells compared with those of control cells. Functional enrichment analysis indicated that up co-regulated genes were related to skeletal system morphogenesis and neuron differentiation and down co-regulated genes were related to steroid/cholesterol/sterol metabolisms. Hub genes (such as IRF1, GBP1, ICAM1, Foxa1, DHCR7, HMGCS2, and MSMO1) were identified. Transcription factors IRF1 and Foxa1 were the targets of miR-130a, miR-17-5p, and miR-20a. PPARGC1A was targeted by miR-29 family, and MSMO1 was the target of miR-23 family. Hub nodes (such as IRF1, GBP1, ICAM1, Foxa1, DHCR7, HMGCS2, and MSMO1) and microRNAs might be used as candidate biomarkers of JFH-1-infected HCC.

show abstract

Functional Polymorphisms of the Lss and Fdft1 Genes in Laboratory Rats

Abstract: Abstract:We previously identified mutant alleles of the lanosterol synthase (Lss)

Cited by 6 publications

References 10 publications

Lanosterol induces mitochondrial uncoupling and protects dopaminergic neurons from cell death in a model for Parkinson's disease

Lanosterol induces mitochondrial uncoupling and protects dopaminergic neurons from cell death in a model for Parkinson's disease

Uncovering Molecular Biomarkers That Correlate Cognitive Decline with the Changes of Hippocampus' Gene Expression Profiles in Alzheimer's Disease

Bioinformatics analysis of hepatitis C virus genotype 2a-induced human hepatocellular carcinoma in Huh7 cells

Contact Info

Product

Resources

About