Abstract:
:The effect of endogenous nitric oxide synthase (NOS) on cardiac contractility and architecture has been a matter of debate. A role for NOS in cardiac hypertrophy has recently been demonstrated by studies which have shown hypertrophic cardiomyopathy (HCM) with altered contractility in constitutive NOS (cNOS) knockout mice. Caveolin-3, a strong inhibitor of all NOS isoforms, is expressed in sarcolemmal caveolae microdomains and binds to cNOS in vivo: endothelial nitric oxide synthase (eNOS) in cardiac myocytes and neuronal nitric oxide synthase (nNOS) in skeletal myocytes. The current study characterized the biochemical and cardiac parameters of P104L mutant caveolin-3 transgenic mice, a model of an autosomal dominant limb-girdle muscular dystrophy (LGMD1C). Transgenic mouse hearts demonstrated HCM, enhanced basal contractility, decreased left ventricular end diastolic diameter, and loss and cytoplasmic mislocalization of caveolin-3 protein. Surprisingly, cardiac muscle showed activation of eNOS catalytic activity without increased expression of all NOS isoforms. These data suggest that a moderate increase in eNOS activity associated with loss of caveolin-3 results in HCM.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Ohsawa Y,Toko H,Katsura M,Morimoto K,Yamada H,Ichikawa Y,Murakami T,Ohkuma S,Komuro I,Sunada Ydoi
10.1093/hmg/ddh014subject
Has Abstractpub_date
2004-01-15 00:00:00pages
151-7issue
2eissn
0964-6906issn
1460-2083pii
ddh014journal_volume
13pub_type
杂志文章abstract::Periodontitis is a widespread, complex inflammatory disease of the mouth, which results in a loss of gingival tissue and alveolar bone, with aggressive periodontitis (AgP) as its most severe form. To identify genetic risk factors for periodontitis, we conducted a genome-wide association study in German AgP patients. W...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp508
更新日期:2010-02-01 00:00:00
abstract::Mitochondria contain a dedicated translation system, which is responsible for the intramitochondrial synthesis of 13 mitochondrial DNA (mtDNA)-encoded polypeptides essential for the biogenesis of oxidative phosphorylation (OXPHOS) complexes I and III-V. Mutations in nuclear genes encoding factors involved in mitochond...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy441
更新日期:2019-05-01 00:00:00
abstract::Gamma glutamyl cysteine ligase (GCL) is the rate-limiting enzyme for intracellular glutathione (GSH) synthesis. The GSH concentration and GCL activity are declining with age in the central nervous system (CNS), and is accompanied by elevated reactive oxygen species (ROS). To study the biological effects of low GSH lev...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddx040
更新日期:2017-04-01 00:00:00
abstract::Brugada syndrome (BrS) is an inherited cardiac arrhythmic disorder that can lead to sudden death, with a prevalence of 1:5000 in Caucasian population and affecting mainly male patients in their third to fourth decade of life. BrS is inherited as an autosomal dominant trait; however, to date genetic bases have been onl...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv302
更新日期:2015-10-15 00:00:00
abstract::Newborn screening (NBS) for medium-chain acyl-CoA dehydrogenase deficiency (MCADD) revealed a higher birth prevalence and genotypic variability than previously estimated, including numerous novel missense mutations in the ACADM gene. On average, these mutations are associated with milder biochemical phenotypes raising...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp079
更新日期:2009-05-01 00:00:00
abstract::A genetic contribution to the pathogenesis of panic disorder has been demonstrated by clinical genetic studies. Molecular genetic studies have focused on candidate genes suggested by the molecular mechanisms implied in the action of drugs utilized for therapy or in challenge tests. One class of drugs effective in the ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/8.4.621
更新日期:1999-04-01 00:00:00
abstract::Huntington's disease (HD) is caused by expansion of the polymorphic polyglutamine segment in the huntingtin protein. Full-length huntingtin is thought to be a predominant HEAT repeat alpha-solenoid, implying a role as a facilitator of macromolecular complexes. Here we have investigated huntingtin's domain structure an...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp524
更新日期:2010-02-15 00:00:00
abstract::Fragile X syndrome, a common cause of intellectual disability and autism, is due to mutational silencing of the FMR1 gene leading to the absence of its gene product, fragile X mental retardation protein (FMRP). FMRP is a selective RNA binding protein owing to two central K-homology domains and a C-terminal arginine-gl...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu586
更新日期:2015-03-15 00:00:00
abstract::Hirschsprung disease (HSCR) is a frequent neurocristopathy characterized by the absence of submucosal and myenteric plexuses in a variable length of the gastrointestinal tract. Pedigrees and segregation analyses suggested the involvement of one or several dominant genes with low penetrance in HSCR. Considering that RE...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/7.9.1449
更新日期:1998-09-01 00:00:00
abstract::Turner syndrome is a complex human disorder that generally associates a 45,X karyotype to a female phenotype presenting with gonadal dysgenesis, short stature and a number of characteristic somatic features. It has been hypothesized that this specific phenotype was the consequence of the haploinsufficiency of some X-l...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/4.9.1565
更新日期:1995-09-01 00:00:00
abstract::Proteins are central to almost all cellular processes, and dysregulation of expression and function is associated with a range of disorders. A number of studies in human have recently shown that genetic factors significantly contribute gene expression variation. In contrast, very little is known about the genetic basi...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds186
更新日期:2012-08-15 00:00:00
abstract::Huntington's disease (HD) is caused by a polyglutamine expansion mutation in the huntingtin protein that confers a toxic gain-of-function and causes the protein to become aggregate-prone. Aggregate-prone proteins are cleared by macroautophagy, and upregulating this process by rapamycin, which inhibits the mammalian ta...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddm294
更新日期:2008-01-15 00:00:00
abstract::Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the epidermal growth factor homology domain repeat A of the low-density lipoprotein receptor (LDLR) at the cell surface and disrupts recycling of the internalized LDLR. As a consequence, the LDLR is rerouted to the lysosomes for degradation. Although PCSK9...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr578
更新日期:2012-03-15 00:00:00
abstract::Immunoglobulins play an essential part in the immune system, and immunoglobulin deficiencies can have profound medical consequences. The genetic control and regulation of the immunoglobulin response is therefore of interest. Previous investigations have identified a number of loci influencing total and specific IgE le...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/7.1.27
更新日期:1998-01-01 00:00:00
abstract::Junctional epidermolysis bullosa with congenital pyloric or duodenal atresia is a distinct variant within this group of autosomal recessive blistering skin diseases. In this study we demonstrate, for the first time, a homozygous mutation in the alpha6 integrin gene (ITGA6) in a family with three affected individuals. ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.5.669
更新日期:1997-05-01 00:00:00
abstract::Von Hippel-Lindau (VHL) disease is a dominantly inherited familial cancer syndrome in which affected individuals have a greatly increased predisposition to the development of haemangioblastomas of the central nervous system and retina, renal cell carcinoma and phaeochromocytoma. The VHL gene has been mapped to chromos...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/2.7.879
更新日期:1993-07-01 00:00:00
abstract::Metabolic control of phenylalanine concentrations in body fluids is essential for cognitive development and executive function. The hepatic phenylalanine hydroxylating system is regulated by the ratio of l-phenylalanine, which is substrate of phenylalanine hydroxylase (PAH), to the PAH cofactor tetrahydrobiopterin (BH...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy079
更新日期:2018-05-15 00:00:00
abstract::Familial exudative vitreoretinopathy (FEVR) belongs to a group of genetically and clinically heterogeneous disorders in retinal vascular development. To date, in approximately 50% of patients with FEVR, pathogenic mutations have been detected in FZD4, LRP5, TSPAN12, NDP and ZNF408. In this study, we identified two het...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw041
更新日期:2016-04-15 00:00:00
abstract::Using a bromodeoxyuridine incorporation method to detect replicated DNA, we studied allele-specific replication of several sites within the human Prader-Willi/Angelman and IGF2/H19 imprinted regions. No obvious allele-specific differences in time of replication were detected at most loci previously reported to replica...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/4.12.2287
更新日期:1995-12-01 00:00:00
abstract::The contribution of BRCA1 and BRCA2 to familial and non-familial forms of breast cancer has been difficult to accurately estimate because of the myriad of potential genetic and epigenetic mechanisms that can ultimately influence their expression and involvement in cellular activities. As one of these potential mechani...
journal_title:Human molecular genetics
pub_type: 临床试验,杂志文章
doi:10.1093/hmg/ddn022
更新日期:2008-05-01 00:00:00
abstract::A recent analysis using family history weighting and co-observation classification modeling indicated that BRCA1 c.594-2A > C (IVS9-2A > C), previously described to cause exon 10 skipping (a truncating alteration), displays characteristics inconsistent with those of a high risk pathogenic BRCA1 variant. We used large-...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw094
更新日期:2016-06-01 00:00:00
abstract::A relationship between fragile sites, specific genomic regions visible as gaps or breaks on cultivated chromosomes, and human disease has been proposed many years ago. Evidence for a role of the ubiquitously expressed common fragile sites characterized by peculiar genome architecture in cancer has been accumulated ove...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddm136
更新日期:2007-10-15 00:00:00
abstract::Karyotypical alteration of chromosome 5 and in particular band 5q13 is a frequent finding in hairy cell leukemia (HCL). We have previously identified a number of candidate genes localized in close proximity to a constitutional inv(5)(p13.1q13.3) breakpoint in one HCL patient. These included beta-hexosaminodase HEXB, f...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddh315
更新日期:2004-12-01 00:00:00
abstract::l-2-Hydroxyglutaric aciduria (l-2-HGA) is characterized by progressive deterioration of central nervous system function including epilepsy and macrocephaly in 50% of cases, and elevated levels of l-2-hydroxyglutaric acid in urine, blood and cerebrospinal fluid (CSF). Nuclear magnetic resonance imaging shows distinct a...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddh300
更新日期:2004-11-15 00:00:00
abstract::Gaucher disease, a prevalent lysosomal storage disease (LSD), is caused by insufficient activity of acid β-glucosidase (GCase) and the resultant glucosylceramide (GC)/glucosylsphingosine (GS) accumulation in visceral organs (Type 1) and the central nervous system (Types 2 and 3). Recent clinical and genetic studies im...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu105
更新日期:2014-08-01 00:00:00
abstract::Type V collagen is a constituent of type I collagen-rich fibrils in many connective tissues and is a regulator of fibril diameter. In tissues, type V collagen is a heterotrimer with the molecular structure: alpha 1(V)2 alpha 2(V) or alpha 1(V) alpha 2(V) alpha 3(V). We report that genomic polymorphisms at the pro alph...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/5.11.1733
更新日期:1996-11-01 00:00:00
abstract::We have constructed a YAC contig containing 54 clones and a minimum of 7 Mbp of human DNA, that maps to bands q34-35 on chromosome 5. The contig was nucleated using FISH mapped cosmid clones shown to flank the t(2;5)(p23;q35) translocation breakpoint in a CD30-positive large cell lymphoma cell line. Thirty of the 54 Y...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/3.1.99
更新日期:1994-01-01 00:00:00
abstract::Huntington's disease (HD) is a dominantly inherited genetic disease caused by mutant huntingtin (htt) protein with expanded polyglutamine (polyQ) tracts. A neuropathological hallmark of HD is the presence of neuronal inclusions of mutant htt. p62 is an important regulatory protein in selective autophagy, a process by ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu522
更新日期:2015-02-15 00:00:00
abstract::Mutation in a growing spectrum of genes is known to either cause or contribute to primary or secondary microcephaly. In primary microcephaly the genetic determinants frequently involve mutations that contribute to or modulate the microtubule cytoskeleton by causing perturbations of neuronal proliferation and migration...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw292
更新日期:2016-11-01 00:00:00
abstract::Losing of ovarian functions prior to natural menopause age causes female infertility and early menopause. Premature ovarian insufficiency (POI) is defined as the loss of ovarian activity before 40 years of age. Known genetic causes account for 25-30% of POI cases, demonstrating the high genetic heterogeneity of POI an...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa153
更新日期:2020-09-29 00:00:00