Abstract:
BACKGROUND:Kanzaki disease (OMIM#104170) is attributable to a deficiency in alpha-N-acetylgalactosaminidase (alpha-NAGA; E.C.3.2.1.49), which hydrolyzes GalNAcalpha1-O-Ser/Thr. Missense mutations, R329W or R329Q were identified in two Japanese Kanzaki patients. Although they are on the same codon, the clinical manifestation was more severe in R329W because an amino acid substitution led to protein instability resulting in structural change, which is greater in R329W than in R329Q. OBJECTIVE:To examine whether the different clinical phenotypes are attributable to the two mutations. METHODS:Plasma alpha-NAGA activity and urinary excreted glycopeptides were measured and three-dimensional models of human alpha-NAGA and its complexes with GalNAcalpha1-O-Ser and GalNAcalpha1-O-Thr were constructed by homology modeling. RESULTS:Residual enzyme activity was significantly higher in the R329Q- than the R329W mutant (0.022+/-0.005 versus 0.005+/-0.001 nmol/h/ml: p<0.05); the urinary ratios of GalNAcalpha1-O-Ser:GalNAcalpha1-O-Thr were 2:10 and 8:10, respectively. GalNAcalpha1-O-Ser/Thr fit tightly in a narrow space of the active site pocket of alpha-NAGA. GalNAcalpha1-O-Thr requires a larger space to associate with alpha-NAGA because of the side chain (CH3) of the threonine residue. CONCLUSION:Our findings suggest that the association of alpha-NAGA with its substrates is strongly affected by the amino acid substitution at R329 and that the association with GalNAcalpha1-O-Thr is more highly susceptible to structural changes. The residual mutant enzyme in R329W could not associate with GalNAcalpha1-O-Thr and GalNAcalpha1-O-Ser. However, the residual mutant enzyme in R329Q catalyzed GalNAcalpha1-O-Ser to some extent. Therefore, the urinary ratio of GalNAcalpha1-O-Ser:GalNAcalpha1-O-Thr was lower and the clinical phenotype was milder in the R329Q mutation. Structural analysis revealed biochemical and phenotypic differences in these Kanzaki patients with the R329Q and R329W mutation.
journal_name
J Dermatol Scijournal_title
Journal of dermatological scienceauthors
Kanekura T,Sakuraba H,Matsuzawa F,Aikawa S,Doi H,Hirabayashi Y,Yoshii N,Fukushige T,Kanzaki Tdoi
10.1016/j.jdermsci.2004.09.005subject
Has Abstractpub_date
2005-01-01 00:00:00pages
15-20issue
1eissn
0923-1811issn
1873-569Xpii
S0923-1811(04)00202-6journal_volume
37pub_type
杂志文章abstract:BACKGROUND:Atopic dermatitis (AD) is characterized by impaired skin barrier function and immune system dysfunction. The expression and role of Yes-associated protein (YAP) in AD are unclear. OBJECTIVE:To characterize the role of the YAP in T cell imbalance and epidermal keratinocyte dysfunction in the pathogenesis of ...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2020.12.004
更新日期:2020-12-18 00:00:00
abstract:BACKGROUND:Th17 is a newly identified effector T cell lineage which plays a central role in many human inflammatory diseases and experimental animal models. Epicutaneous sensitization with a protein antigen has been proven to induce a Th2-predominant immune response and lead to development of atopic diseases in a murin...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2008.12.011
更新日期:2009-06-01 00:00:00
abstract:BACKGROUND:Reactive oxygen species (ROS)-induced mitochondrial damage aggravates oxidative stress and activates mitochondrial apoptosis pathway to mediate melanocyte death. However, the repair mechanisms underlying damaged mitochondria of melanocytes remain unclear. Accumulative evidence has revealed that the aryl hydr...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2019.09.001
更新日期:2019-10-01 00:00:00
abstract::Matrix metalloproteinases (MMPs) play an important role in tumor invasion and metastasis. Enhanced expression of matrix metalloproteinase-2 (MMP-2) has been demonstrated in dermatofibroma (DF) and malignant fibrous histiocytoma (MFH). MMP-2 has been shown to be activated by membrane-type MMPs (MT-MMPs). To study the r...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/s0923-1811(01)00159-1
更新日期:2002-02-01 00:00:00
abstract:BACKGROUND:Foot ulcers are one of the main diabetes complications due to its high frequency and difficulty of complete healing. There are several factors that participate in diabetic ulcers development and limited information exists about the role of antimicrobial peptides (AMP) in its pathogenesis. OBJECTIVE:The aim ...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2011.09.013
更新日期:2012-01-01 00:00:00
abstract::Propionibacterium acnes (P. acnes) causes an inflammatory acne that is characterized by massive neutrophilic infiltration. IL-8 is thought to play an important role in the pathophysiology of P. acnes, although the mechanisms by which P. acnes up-regulates the release of IL-8, a neutrophilic chemokine, from target cell...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/s0923-1811(02)00013-0
更新日期:2002-08-01 00:00:00
abstract:BACKGROUND:Retinoic acid-inducible gene-I (RIG-I) is a member of the DExH/D box family proteins and designated as a putative RNA helicase, which plays various roles in gene expression and cellular functions in response to a variety of RNA viruses. OBJECTIVE:The present study was designed to investigate the effects of ...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2006.11.003
更新日期:2007-02-01 00:00:00
abstract::Stem cells are fascinating because of their potential in regenerative medicine. Stem cell homeostasis has been thought to be mainly regulated by signals from their adjacent micro-environment named the "stem cell niche". However, recent studies reveal that there can be multiple layers of environmental controls. Here we...
journal_title:Journal of dermatological science
pub_type: 杂志文章,评审
doi:10.1016/j.jdermsci.2012.02.007
更新日期:2012-04-01 00:00:00
abstract:BACKGROUND:Hyperpigmentation is aesthetic undesirable. Sesamol and the standard antimelanogenic agent (kojic acid) were shown to hinder melanogenesis by blocking tyrosinase and reducing melanin content. OBJECTIVE:The FTIR microspectroscopy was used in an attempt to find a novel method to define biological alternation ...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2013.11.002
更新日期:2014-03-01 00:00:00
abstract:BACKGROUND:IL36RN mutation has been identified as one pathogenesis of generalized pustular psoriasis, but the existence of GPP patients without mutation makes this controversial. OBJECTIVE:Our study aimed at assessing the differences in clinical profiles of children with GPP, with and without IL36RN mutation. METHODS...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2016.11.008
更新日期:2017-03-01 00:00:00
abstract:BACKGROUND:Rutin, due to its polyphenolic structure, has antioxidant properties and can be used as a cytoprotective compound against UV-induced effects on skin cells. OBJECTIVE:The aim of this study was to examine the effect of rutin on proteomic profile in human skin fibroblasts irradiated with UV dose that induces a...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2018.02.002
更新日期:2018-06-01 00:00:00
abstract::Genetically engineered mouse models are invaluable to investigators in nearly all areas of biomedical research. The use of genetically engineered mice has allowed researchers to explore fundamental functions of genes in a mammal that shares substantial similarities with human physiology and pathology. Genetically engi...
journal_title:Journal of dermatological science
pub_type: 杂志文章,评审
doi:10.1016/j.jdermsci.2008.03.012
更新日期:2008-10-01 00:00:00
abstract:BACKGROUND:The molecular pathogenesis underlying recurrent exacerbations of atopic dermatitis (AD) is unclear. Some peripheral CCR4(+) and CCR7(+) helper memory T cells express the specific homing receptor, sialyl 6-sulfo Lewis X (G152 glycan). This glycan loses receptor activity via cyclization of its sialic acid moie...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2012.09.015
更新日期:2012-12-01 00:00:00
abstract::Dermatitis herpetiformis is characterised by granular IgA precipitates in the papillary dermis. In contrast to other autoimmune blistering diseases, where tissue-deposited and circulating autoantibodies recognise the same target within the skin, in dermatitis herpetiformis a serum IgA reacting with a component of the ...
journal_title:Journal of dermatological science
pub_type: 杂志文章,评审
doi:10.1016/j.jdermsci.2003.11.004
更新日期:2004-04-01 00:00:00
abstract::Temperature influences the stratum corneum adsorption of several topically applied compounds. This study was designed to evaluate the influence of the temperature on the stratum corneum adsorption of 3 UV filters. The UV filters were solubilized in two vehicles, an emulsion gel and petroleum jelly and applied at respe...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/s0923-1811(01)00100-1
更新日期:2001-10-01 00:00:00
abstract::Hair follicle morphogenesis and regeneration depend on intensive but well-orchestrated interactions between epithelial and mesenchymal components. Accordingly, the enhancement of this crosstalk represents a promising approach to achieve successful bioengineering of human hair follicles. The present article summarizes ...
journal_title:Journal of dermatological science
pub_type: 杂志文章,评审
doi:10.1016/j.jdermsci.2013.02.004
更新日期:2013-05-01 00:00:00
abstract:BACKGROUND:We recently reported use of photodynamic therapy (PDT) for treating keloid disease (KD). However, in view of high recurrence rates post any treatment modality, adjuvant therapies should be considered. Additionally, we previously demonstrated the effect of a novel electrical waveform, the degenerate wave (DW)...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2011.08.012
更新日期:2011-12-01 00:00:00
abstract:BACKGROUND:Aberrant expression of microRNAs (miRNAs) has been implicated in oncogenesis of various tumors and primary cutaneous T cell lymphomas. Dicer, a ribonuclease III-like enzyme is essential for miRNA processing. OBJECTIVE:We initiated a retrospective study to characterize the alterations in the expression profi...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2011.08.011
更新日期:2011-12-01 00:00:00
abstract::Isolated normal human melanocytes became enlarged and more dendritic in association with an increase in the activity of tyrosinase and the amount of b-locus protein when they were cultured with 0.1-10 microM histamine in vitro. However, histamine did not exert a proliferative effect on them. The stimulatory effect of ...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/0923-1811(93)90005-a
更新日期:1993-10-01 00:00:00
abstract:BACKGROUND:Atopic dermatitis (AD) is a chronic inflammatory skin disease that often cannot be completely controlled by modern medicine. Since multiple factors are intricately involved in the pathogenesis of AD, wide-ranging research is required for further advancement of AD treatment. Epidermal keratinocytes are the fo...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2017.06.017
更新日期:2017-11-01 00:00:00
abstract:BACKGROUND:Ultraviolet B (UVB) radiation is a major cause of skin photodamage, including the damage associated with photodermatoses, aging, and cancer. Although many studies have shown that red light has photoprotective effects on skin, the mechanisms underlying these effects are still poorly understood. OBJECTIVE:The...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2019.03.003
更新日期:2019-05-01 00:00:00
abstract::Psoriatic involved epidermis has been characterized by a defective beta-adrenergic adenylate cyclase response. It is also characterized by increased cholera toxin- and forskolin-induced cyclic AMP accumulations. Due to the fact that receptor signals are transduced to adenylate cyclase through guanine nucleotides bindi...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/s0923-1811(97)00069-8
更新日期:1998-05-01 00:00:00
abstract::Injury to vessel walls, especially microvascular damage due to free radicals, has been a focus of interest concerning the pathogenesis of systemic sclerosis. Excess reactive oxygen species may induce antioxidant defenses. We therefore measured plasma superoxide dismutase (SOD) activity in patients with systemic sclero...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/0923-1811(95)00441-6
更新日期:1996-03-01 00:00:00
abstract::An immunoperoxidase technique was performed to detect keratinolytic proteinase (KPase) in sections of the skin taken from guinea pigs infected with Microsporum canis and in cultured M. canis using polyclonal antisera to purified KPase. Of tissue samples from guinea pigs infected with M. canis, all sections of erythema...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/0923-1811(90)90015-6
更新日期:1990-11-01 00:00:00
abstract:BACKGROUND:The exact mechanism of the inflammatory changes occurring during the development of Behçet's disease (BD) remains unclear. OBJECTIVE:We investigated the role of classical (M1) and alternative (M2) activation of macrophages in a herpes simplex virus (HSV)-induced BD mouse model. METHODS:The classical vs. al...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2013.11.001
更新日期:2014-03-01 00:00:00
abstract::In order to disclose the possible disturbance in regulation of p21ras function in neurofibromatosis type 1, we investigated the recovery from the quiescent to cycling states of the cell cycle in the skin fibroblasts of the patients. When cells cultured in serum-dependent medium are deprived of the serum, these go into...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/0923-1811(94)90082-5
更新日期:1994-04-01 00:00:00
abstract::Epidermolysis bullosa simplex associated with late onset of muscular dystrophy has been found to show defective expression of plectin, an intracytoplasmic protein in hemidesmosomes. In this report, we examined ability of cell-to-matrix attachment of cultured keratinocytes derived from a case with this disease by vario...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/s0923-1811(00)00100-6
更新日期:2000-12-01 00:00:00
abstract:BACKGROUND:The inducement of Th1 cell-mediated immune response, possibly brought about through bacterial stimulation, may serve to control atopic disorders such as atopic dermatitis (AD). The streptococcal preparation, OK-432, has been shown a potent Th1 inducer through the action of IL-12. NC/Nga mice under ordinary c...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2004.06.006
更新日期:2004-09-01 00:00:00
abstract::Psoriatic skin lesions contain HLA-DR positive T lymphocytes, and other activation antigens, which suggest that the T cells may be producing lymphokines. Gamma interferon is produced by activated T cells, and its presence in psoriasis has been inferred by the lesional keratinocyte expression of 3 gamma interferon-indu...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/0923-1811(91)90019-t
更新日期:1991-03-01 00:00:00
abstract::Extracted human terminal and vellus hair follicles were prepared by EDTA and examined by light and electron microscopes. These samples were morphologically well preserved and enabled us to observe 3-dimensional (3-D) views of the outer surfaces of hair follicles. Interestingly, the bulge areas of terminal and vellus h...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/0923-1811(94)90030-2
更新日期:1994-07-01 00:00:00