Shuren Wang

Homocysteine-induced extracellular superoxide dismutase and its epigenetic mechanisms in monocytes

SUMMARY Although a modest homocysteine (Hcy) elevation is associated with an increased cardiovascular risk, the underlying mechanisms whereby Hcy triggers the accumulation of cholesterol and the roles of the extracellular superoxide dismutase (EC-SOD) in the development of foam cells have not yet been elucidated. In this study, we found both increased numbers of foam cells and an accumulation of cholesterol, and the H2O2 and oxidized low-density lipoprotein content also increased. Levels of EC-SOD were significantly suppressed by Hcy, however, while 5-azacytidine (AZC), a potent DNA methyltransferase (DNMT) inhibitor, increased the expression of EC-SOD. A quantitative real-time PCR of EC-SOD revealed that Hcy (100 μmol l–1) accelerates DNA methylation of EC-SOD, but selectively increases the activity of DNA methyl transferase 1 (DNMT1). It showed that Hcy can reduce binding of methyl CpG and binding protein 2 (MeCP2) but has no effect on the activity of DNMT3. Moreover, chromatin immunoprecipitation assays demonstrated that Hcy increased the binding of acetylated histone H3 and H4 in monocytes. Based on the fact that the binding of MeCP2 with the EC-SOD was completely suppressed by AZC and trichostatin A [TSA, a histone deacetylase (HDAC) inhibitor], it is indicated that DNA methylation and HDAC mediate the binding of MeCP2 with EC-SOD gene. In conclusion, the study found that Hcy accelerates the development of foam cells by repressing EC-SOD transcription, and that Hcy exerts this function by upregulating DNA methylation via suppression of HDAC activity and increased DNMT1 activity.

A novel large deletion of the DOCK8 gene in a Chinese family with autosomal-recessive hyper-IgE syndrome.

Autosomal‐recessive hyper‐IgE syndrome (AR‐HIES; OMIM 243700) is a rare primary immunodeficiency disorder mainly caused by mutations in the dedicator of cytokinesis‐8 (DOCK8) gene. DOCK8 is highly expressed in the immune system and plays important roles in regulation of lymphocyte functions.

A novel case of delayed congenital diffuse melanosis: immune dysfunction?

Editor Congenital diffuse melanosis is a rare recessive genetic disease characterized by the diffuse grey-brownish hyperpigmentation of the skin. To the best of our knowledge, the reports of this disease in the world are less than 10 cases, and each case had an early childhood onset. We herein describe a novel case of delayed congenital diffuse melanosis with onset in adolescent stage, which has not been reported before. A 20-year-old Chinese young man came to us for a 5-year history of slow-moving but progressing hyperpigmentation of trunk and proximal portion of limbs beginning from abdominal skin of navel surrounding areas, with no experience of erythema, oedema, or pruritus. Physical examination revealed generalized, diffused, uniform grey-brownish hyperpigmentation of trunk, neck and proximal portion of limbs, with a few dispersed normal-colour spots and a less hyperpigmented line in neck and abdominal region, respectively (Fig. 1a,b). The skin’s texture, hair and sweat secretion were normal. He was otherwise healthy and had no history of drug intake, toxic agents contact, inflammatory condition, discoloration of urine or photosensitivity prior to the onset of skin lesions. His family history was unremarkable. The hepatitis B surface antigen and HIV screening were negative. Other than normal level of the trace element of blood as well as functions of liver and adrenal cortex, the immune test showed ANA (++1 : 1000 dilute, speckled). The pathological report of the patient’s abdominal pigmented skin showed an increasing number of melanophages in the superficial layer of dermis with a mild liquefaction degeneration of basal cells (Fig. 2a). The histopathological analysis of the specimen stained with dihydroxyphenylalanine (DOPA) (Fig. 2b) and Masson Fontana-Ponceau method (Fig. 2c) showed that the positive cells in the basal membrane were apparently increased as well as the melanin increased in the stratum spinosum to stratum basale. We have been treating our patient symptomatically for about 1 year with vitamin C, and glutathione, but the effect is not so remarkable. The clinical features of our patient’s lesion can be also distinguished from the four typical types of diffuse pigmentation disease including dyschromatosis universalis hereditaria (DUH), familial progressive hyperpigmentation (FPH), Riehl’s melanosis and universal acquired melanosis (Carbon baby). Most areas of hyperpigmentation of both DUH and FPH are not uniform, which are excluded in this case. Riehl’s melanosis almost exhibits the hyperpigmentation of the sun-exposed area, while the present patient’s skin of sun-exposed areas including face as well as distal of limbs seemed normal. Universal acquired melanosis describes progressive diffuse hyperpigmentation in infancy without any area of reticulate pigmentationin. However, in this case, a small part of the hyperpigmented area (cervical and abdominal) is mixed with normal-colour spots or less hyperpigmented line. The mechanism of the hyperpigmentation is not known yet to date. Schwartz et al. reported a congenital melanocytosis with myelomeningocele and hydrocephalus, and they referred to possibility of a relation between this disease and neuroectodermal malformation. It is noteworthy that the patient has an obvious immunological derangement with the antinuclear antibody (ANA) up-regulation (++ 1 : 1000 dilute). Therefore, we suppose that the cause that arouses the hyperpigmentation may be related to immune dysfunction in some delayed or acquired cases. (a)

Retraction: Homocysteine-induced extracellular superoxide dismutase and its epigenetic mechanisms in monocytes.

Yideng, J., Jianzhong, J., Jiantuan, X., Jun, C., Nan, L., Guizhong, L. and Shuren, W. (2008). J. Exp. Biol . 211 , [911-920][1]. After careful examination of the above paper published in The Journal of Experimental Biology ([Yideng et al., 2008][2]), we have realised that we made a number of