Naofen has recently been identified from the rat brain/spinal cord cDNA library as a substance reactive against an anti-shigatoxin (Stx)-2 antibody. Naofen mRNA is composed of 4620 nucleotides and encodes 1170 amino acids. Naofen contains four WD-repeat domains in its N-terminus and is ubiquitously distributed in many tissues of the rat. Tumor necrosis factor (TNF)-alpha enhanced the expression of naofen mRNA in HEK293 cells in a dose-dependent manner. Furthermore, naofen siRNA, which predominantly knocked down the expression of naofen mRNA, significantly reduced both TNF-alpha-induced caspase-3 activation and apoptosis in HEK293 cells. Overexpression of naofen in HEK293 cells (FLAG-NF) spontaneously induced caspase -3 activation and apoptosis, and showed extremely high susceptibility to TNF-alpha-induced apoptosis. These results indicated that naofen may function as a novel modulator activating caspase-3, and promoting TNF-alpha-stimulated apoptosis.
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Naofen promotes TNF-α-mediated apoptosis of hepatocytes by activating caspase-3 in lipopolysaccharide-treated rats.
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Jun-Hua Fan, Guo-Duo Tang, Hai-Xing Jiang, Department of Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
Aim: To investigate whether naofen is involved in tumor necrosis factor (TNF)-α-mediated apoptosis of hepatocytes induced by lipopolysaccharide (LPS).
Methods: In vivo, rats were treated with LPS or anti-TNF-α antibody, whereas in vitro, primary hepatocytes and Kupffer cells (KCs) were separately isolated from rat livers using collagenase perfusion, and primary hepatocytes were cultured in medium containing LPS or TNF-α, or in conditioned medium from LPS-treated KCs (KC-CM)/KC-CM + anti-TNF-α antibody. Naofen and TNF-α mRNA expression was examined by real-time reverse transcription-polymerase chain reaction.
Exome sequencing identifies WDR35 variants involved in Sensenbrenner syndrome.
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September 2010
Department of Human Genetics, Institute for Genetic and Metabolic Disorders, Radboud University Nijmegen Medical Centre, The Netherlands.
Sensenbrenner syndrome/cranioectodermal dysplasia (CED) is an autosomal-recessive disease that is characterized by craniosynostosis and ectodermal and skeletal abnormalities. We sequenced the exomes of two unrelated CED patients and identified compound heterozygous mutations in WDR35 as the cause of the disease in each of the two patients independently, showing that it is possible to find the causative gene by sequencing the exome of a single sporadic patient. With RT-PCR, we demonstrate that a splice-site mutation in exon 2 of WDR35 alters splicing of RNA on the affected allele, introducing a premature stop codon.
View Article and Find Full Text PDFEnhanced expression of naofen in kidney of streptozotocin-induced diabetic rats: possible correlation to apoptosis of tubular epithelial cells.
Clin Exp Nephrol
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Department of Anesthesiology, Aichi Medical University School of Medicine, Nagakute, Aichi-gun, Aichi, 480-1195, Japan.
Background: Hyperglycemia/high glucose may induce apoptosis in diabetic kidney, but the mechanism is not fully understood. Naofen was found as a Shiga toxin (Stx)-2-related protein. Based on renal dysfunction in infection with Stx-producing Escherichia coli and on participation of naofen in apoptosis of human embryonic kidney cells, the present study was undertaken to investigate the mechanism of renal dysfunction in diabetes mellitus with particular reference to naofen.
View Article and Find Full Text PDFNaofen, a novel WD40-repeat protein, mediates spontaneous and tumor necrosis factor-induced apoptosis.
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Department of Pharmacology, Aichi Medical University School of Medicine, Nagakute, Aichi-gun, Aichi Pref 480-1195, Japan.
Naofen has recently been identified from the rat brain/spinal cord cDNA library as a substance reactive against an anti-shigatoxin (Stx)-2 antibody. Naofen mRNA is composed of 4620 nucleotides and encodes 1170 amino acids. Naofen contains four WD-repeat domains in its N-terminus and is ubiquitously distributed in many tissues of the rat.
View Article and Find Full Text PDFRole of naofen, a novel WD repeat-containing protein, in reducing nitric oxide-induced relaxation.
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Department of Pharmacology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.
1. Naofen, a novel WD40 repeat domain-containing protein, has recently been found in the intracellular compartment. The aim of the present study was to determine whether naofen affects thoracic aortic vascular reactivity in normotensive and hypertensive rats and whether naofen is present in the thoracic aorta.
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