Identification of the Human cDNA for New Survival/Evasion Peptide (DSEP): Studies in Vitro and in Vivo of Overexpression by Neural Cells

Cunningham, Timothy J.; Jing, Huiyan; Akerblom, Ingrid; Morgan, R.M.L.; Fisher, Timothy S.; Neveu, Mark J.

doi:10.1006/exnr.2002.7979

Cited by 40 publications

(34 citation statements)

References 29 publications

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“…It has been reported that the N-terminal 30 amino acid peptide of DCD, which is known as either survivalpromoting peptide, diffusible survival evasion peptide (DSEP), or Y-P 30 (Cunningham et al 1998(Cunningham et al , 2002, promotes neural cell survival under oxidative conditions. Y-P 30 is a product of the same region of DCD as the core peptide of proteolysis-inducing factor (PIF) that has been identified as a cachectic factor that was purified from cachexia-inducing murine tumors and urine of patients with pancreatic cancer that experienced weight loss (Todorov et al 1996, Wigmore et al 2000.…”

Section: Introductionmentioning

confidence: 99%

Effect of dermcidin, an antimicrobial peptide, on body fat mobilization in normal mice

Kim¹,

Ka²,

Moon³

et al. 2008

Journal of Endocrinology

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Dermcidin (DCD), an antimicrobial peptide that is secreted by sweat glands, is reportedly a human homolog of mouse proteolysis-inducing factor. This study was conducted to investigate the effect of DCD on body fat mobilization. The expression level of DCD in the livers of Ad-DCD-injected mice was higher than in those of Ad-b-galactosidase (Ad-bgal)-injected mice 7 days after injection. In addition, injection with the Ad-DCD virus led to decreased body weight and epididymal fat mass when compared with controls. The plasma triglyceride level was decreased, whereas the free fatty acid and glycerol levels were increased in the Ad-DCDinjected group. Epididymal adipose tissues obtained from Ad-DCD-injected mice consisted of smaller adipocytes than tissues obtained from Ad-b-gal-injected mice. The gene expression profiles revealed an upregulation of hormonesensitive lipase and adipose fatty acid-binding protein, both of which are involved in adipocyte lipolysis, in Ad-DCDinjected mice, and this lipolytic effect of DCD paralleled the increase of circulating tumor necrosis factor-a (TNF-a) level that was observed. The perilipin levels in adipose tissue were decreased in Ad-DCD-injected mice when compared with those of the control mice. Taken together, these results suggest that DCD-mediated body fat reduction might occur as a result of TNF-a-induced downregulation of perilipin in adipose tissue.

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Section: Introductionmentioning

confidence: 99%

Effect of dermcidin, an antimicrobial peptide, on body fat mobilization in normal mice

Kim¹,

Ka²,

Moon³

et al. 2008

Journal of Endocrinology

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“…The Y-P30 peptide was present in medium conditioned by human retinoblastoma cells and a mouse hippocampal cell line exposed to hydrogen peroxide. Y-P30 was subsequently identified as comprising part of a 110 amino acid polypeptide which Cunningham et al, (2002) named diffusible survival evasion peptide (DSEP). DSEPoverexpressing neuronal cells were also found to have an increased resistance to oxidative stress (Cunningham et al, 2002).…”

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confidence: 99%

“…The protein products of the 110 amino acid DCD polypeptide (Figure 1) include the 47 amino acid DCD-1 peptide (a skin antimicrobial) (Schittek et al, 2001) and the 30 amino acid proteolysis-inducing factor-core peptide (PIF-CP) (Lowrie et al, 2006), the latter of which is identical to Y-P30 (Cunningham et al, 1998). The DCD protein (Schittek et al, 2001) is identical to human cachexia-associated protein (HCAP) (Akerblom and Murry, 1998) and DSEP (Cunningham et al, 2002). Furthermore, when glycosylated, PIF is reported to behave as a factor in cancer cachexia (Todorov et al, 1996).…”

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confidence: 99%

Variation in dermcidin expression in a range of primary human tumours and in hypoxic/oxidatively stressed human cell lines

et al. 2008

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Dermcidin acts as a survival factor in a variety of cancer cell lines under hypoxia or oxidative stress. The aim of this study was to evaluate dermcidin expression in cell lines following simulation of tumour microenvironmental conditions and in a range of primary tumours. Tumour tissues were collected from patients with oesophageal (28 samples), gastric (20), pancreatic (five), bile duct (one) and prostatic (52) carcinomas as well as 30 benign tissue samples, for assessment of dermcidin mRNA levels using real-time PCR. Dermcidin expression was assessed in prostatic and pancreatic cancer cell lines, with and without induction of hypoxia or oxidative stress. Dermcidin mRNA expression was very low or absent in both unstressed and stressed prostate cell lines. None of the primary prostate tissue, benign or malignant, expressed dermcidin mRNA. Only two (4%) of the gastro-oesophageal cancer samples expressed moderate quantities of dermcidin mRNA. However, three (60%) of the pancreatic cancer samples and the single cholangiocarcinoma specimen had moderate/high levels of dermcidin expression. Of the two pancreatic cancer cell lines, one expressed dermcidin moderately but neither showed a response to hypoxia or oxidative stress. Expression of dermcidin in human primary tumours appears highly variable and is not induced substantially by hypoxia/oxidative stress in cell line model systems. The relationship of these findings to dermcidin protein levels and cell survival remains to be determined.

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“…Dermcidin has been identified as a candidate oncogene in breast cancer and stable transfection has been shown to stimulate cell growth and inhibit menadione-induced cell death, as assessed by cell counting (Porter et al, 2003). Stable transfection of dermcidin has also been demonstrated to improve the survival of neuronal cells subjected to oxidative stress with H 2 O 2 (Cunningham et al, 2002), and it is feasible that these effects are due to the activity of Y-P30. The mechanism by which this peptide improves survival appears to involve a central, calcineurin-like phosphatase domain (Cunningham et al, 1998).…”

mentioning

confidence: 99%

Dermcidin expression in hepatic cells improves survival without N-glycosylation, but requires asparagine residues

et al. 2006

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Proteolysis-inducing factor, a cachexia-inducing tumour product, is an N-glycosylated peptide with homology to the unglycosylated neuronal survival peptide Y-P30 and a predicted product of the dermcidin gene, a pro-survival oncogene in breast cancer. We aimed to investigate whether dermcidin is pro-survival in liver cells, in which proteolysis-inducing factor induces catabolism, and to determine the role of potentially glycosylated asparagine residues in this function. Reverse cloning of proteolysis-inducing factor demonstrated B100% homology with the dermcidin cDNA. This cDNA was cloned into pcDNA3.1 þ and both asparagine residues removed using site-directed mutagenesis. In vitro translation demonstrated signal peptide production, but no difference in molecular weight between the products of native and mutant vectors. Immunocytochemistry of HuH7 cells transiently transfected with V5-His-tagged dermcidin confirmed targeting to the secretory pathway. Stable transfection conferred protection against oxidative stress. This was abrogated by mutation of both asparagines in combination, but not by mutation of either asparagine alone. These findings suggest that dermcidin may function as an oncogene in hepatic as well as breast cells. Glycosylation does not appear to be required, but the importance of asparagine residues suggests a role for the proteolysis-inducing factor core peptide domain.

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Identification of the Human cDNA for New Survival/Evasion Peptide (DSEP): Studies in Vitro and in Vivo of Overexpression by Neural Cells

Cited by 40 publications

References 29 publications

Effect of dermcidin, an antimicrobial peptide, on body fat mobilization in normal mice

Effect of dermcidin, an antimicrobial peptide, on body fat mobilization in normal mice

Variation in dermcidin expression in a range of primary human tumours and in hypoxic/oxidatively stressed human cell lines

Dermcidin expression in hepatic cells improves survival without N-glycosylation, but requires asparagine residues

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