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DCD  -  dermcidin

Homo sapiens

Synonyms: AIDD, DCD-1, DSEP, Dermcidin, HCAP, ...
 
 
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Disease relevance of DCD

  • Putative high- and low-affinity receptors for DCD are present on the cell surface of breast carcinomas and neurons of the brain [1].
  • Expression of DCD in breast cancer cells promotes cell growth and survival and reduces serum dependency [1].
  • Deficiency of dermcidin-derived antimicrobial peptides in sweat of patients with atopic dermatitis correlates with an impaired innate defense of human skin in vivo [2].
  • Interestingly, although all naturally processed DCD peptides can adopt an alpha-helical conformation in solvents, they have a diverse and partially overlapping spectrum of activity against gram-positive and gram-negative bacteria [3].
  • This trial evaluated the dose response of DCD in patients with chronic stable angina pectoris [4].
 

Psychiatry related information on DCD

 

High impact information on DCD

  • Dermcidin: a novel human antibiotic peptide secreted by sweat glands [9].
  • The structure defines the hydrophobic pocket termed the "PIF-pocket", which plays a key role in mediating the interaction and phosphorylation of certain substrates such as S6K1 [10].
  • Interestingly, close to the PIF-pocket in PDK1, there is an ordered sulfate ion, interacting tightly with four surrounding side chains [10].
  • PIF was used to successfully image iNOS expressed in RAW264.7 cells, HEK293T cells, human A549 epithelial cells, and freshly obtained human lung epithelium [11].
  • Their derived amino acid sequences and that previously determined for the PIF protein completely explain the electrophoretic phenotypes of the acidic proline-rich proteins (PRPs) Pa, Db, and PIF [12].
 

Chemical compound and disease context of DCD

 

Biological context of DCD

  • Part of the survival advantage of DSEP overexpressors may be due to their attenuated response to all-trans-retinoic acid, which regulates differentiation and apoptosis of several cell types including neural and immune cells [16].
  • DCD is unaffected by the ATP synthase inhibitor oligomycin but is inhibited by the further addition of a respiratory chain inhibitor to depolarize the mitochondria and inhibit mitochondrial calcium accumulation without depleting ATP [Budd and Nicholls (1996) J. Neurochem. 67, 2282-2291] [17].
  • CONCLUSIONS: These preliminary data suggest that DCD may be a useful urodynamic parameter to predict and optimize therapy with a-blockade [18].
  • After a variable latent period, a secondary, irreversible increase in calcium occurs (delayed calcium deregulation, DCD) which precedes and predicts subsequent cell death [19].
  • Graft survival rates at 1, 3, 5, and 10 years were 90.8%, 86.5%, 77.8%, and 69.0%, respectively, compared with 89% at 1 year and 80% at 3 years reported for DCD by the SRTR in which almost 30% of the grafts underwent PP [20].
 

Anatomical context of DCD

  • Elevated cytoplasmic calcium is not excitotoxic as long as mitochondria are depolarized; alternative substrates do not rescue cells about to undergo DCD, suggesting that glycolytic failure is not involved [17].
  • The mitochondrial generation of superoxide anions is enhanced during glutamate exposure and a working hypothesis is that DCD may be caused by oxidative damage to calcium extrusion pathways at the plasma membrane [17].
  • The data convincingly show that irrespective of charge the different DCD peptides are not able to permeabilize bacterial membranes [3].
  • OBJECTIVES: To investigate whether DCD expression is induced under inflammatory conditions in epidermal keratinocytes [13].
  • Besides these confirmatory results, two suggestions emerged from the study: (1) The relative number of cells: osteoclast density (OI) and osteoblasts (Ob/OID) appears to be lower, not only than NDCD values but also lower than N values (OI = 0.04 c/mm. in DCD, 0.31 in NDCD, and 0.14 in N; Ob/OID = 5.58% in DCD, 14.6 in NDCD and 22.12 +/- 9% m N) [21].
 

Associations of DCD with chemical compounds

  • Cultured cerebellar granule cells demonstrate delayed calcium de-regulation (DCD) followed by necrosis upon exposure to glutamate [17].
  • According to the experimental data, deltic acid dimethyl ester is produced by decarbonylation of the initially formed bisketene and not by direct CO extrusion from DCD [22].
  • (2) Dynamic behavior in tetracycline based studies disclosed the appearance of two populations of DCD: a subgroup of preserved calcification dynamics with values not quite different than the NDCD group and a subgroup with a significant derangement of mineralization with no measurable bone trabecular dynamics [21].
  • However, mitochondrial depolarisation (and hence inhibition of mitochondrial calcium accumulation) without parallel ATP depletion (oligomycin plus either rotenone or antimycin A) strongly protects the cells against DCD [19].
  • Given the limited side effects, a trial of L-carnitine with ongoing evaluation of beneficial effect is a reasonable therapeutic option for chronic dialysis patients with clinical conditions related to DCD [23].
 

Other interactions of DCD

  • In humans, eccrine appendages express DCD and CAMP, genes encoding proteins processed into the antimicrobial peptides dermcidin and LL-37 [24].
 

Analytical, diagnostic and therapeutic context of DCD

  • Therefore, we performed semiquantitative and quantitative analyses of DCD peptides in sweat of AD patients and healthy subjects using surface-enhanced laser desorption ionization time-of-flight mass spectrometry and ELISA [2].
  • RESULTS: The mean ratio of myocardial counts to lung counts was lower on the DCD images (2.77 +/- 1.12) than on the UHGP SPECT images (3.69 +/- 0.98) (P < 0.05) [25].
  • Finally, immunoelectron microscopy studies indicated that DCD peptides are able to bind to the bacterial surface; however, signs of membrane perturbation were not observed [3].
  • Furthermore, using carboxyfluorescein-loaded liposomes, membrane permeability studies and electron microscopy we investigated whether DCD peptides are able to permeabilize bacterial membranes [3].
  • Using surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF-MS) and reversed-phase high-pressure liquid chromatography analysis, we identified in eccrine sweat 14 proteolytically processed DCD peptides [26].

References

  1. A neural survival factor is a candidate oncogene in breast cancer. Porter, D., Weremowicz, S., Chin, K., Seth, P., Keshaviah, A., Lahti-Domenici, J., Bae, Y.K., Monitto, C.L., Merlos-Suarez, A., Chan, J., Hulette, C.M., Richardson, A., Morton, C.C., Marks, J., Duyao, M., Hruban, R., Gabrielson, E., Gelman, R., Polyak, K. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  2. Deficiency of dermcidin-derived antimicrobial peptides in sweat of patients with atopic dermatitis correlates with an impaired innate defense of human skin in vivo. Rieg, S., Steffen, H., Seeber, S., Humeny, A., Kalbacher, H., Dietz, K., Garbe, C., Schittek, B. J. Immunol. (2005) [Pubmed]
  3. Naturally processed dermcidin-derived peptides do not permeabilize bacterial membranes and kill microorganisms irrespective of their charge. Steffen, H., Rieg, S., Wiedemann, I., Kalbacher, H., Deeg, M., Sahl, H.G., Peschel, A., Götz, F., Garbe, C., Schittek, B. Antimicrob. Agents Chemother. (2006) [Pubmed]
  4. Dose-response evaluation of once-daily therapy with a new formulation of diltiazem for stable angina pectoris. Diltiazem CD Study Group. Thadani, U., Glasser, S., Bittar, N., Beach, C.L. Am. J. Cardiol. (1994) [Pubmed]
  5. Co-existing psychiatric problems in ADHD in the ADORE cohort. Steinhausen, H.C., N??vik, T.S., Baldursson, G., Curatolo, P., Lorenzo, M.J., Rodrigues Pereira, R., Ralston, S.J., Rothenberger, A. European child & adolescent psychiatry (2006) [Pubmed]
  6. The preparation of reach-to-grasp movements in adults, children, and children with movement problems. Mon-Williams, M., Tresilian, J.R., Bell, V.E., Coppard, V.L., Nixdorf, M., Carson, R.G. The Quarterly journal of experimental psychology. A, Human experimental psychology. (2005) [Pubmed]
  7. Evaluation of a screening instrument for developmental coordination disorder. Hay, J.A., Hawes, R., Faught, B.E. The Journal of adolescent health : official publication of the Society for Adolescent Medicine. (2004) [Pubmed]
  8. The relationship between motor control and phonology in dyslexic children. Ramus, F., Pidgeon, E., Frith, U. Journal of child psychology and psychiatry, and allied disciplines. (2003) [Pubmed]
  9. Dermcidin: a novel human antibiotic peptide secreted by sweat glands. Schittek, B., Hipfel, R., Sauer, B., Bauer, J., Kalbacher, H., Stevanovic, S., Schirle, M., Schroeder, K., Blin, N., Meier, F., Rassner, G., Garbe, C. Nat. Immunol. (2001) [Pubmed]
  10. High resolution crystal structure of the human PDK1 catalytic domain defines the regulatory phosphopeptide docking site. Biondi, R.M., Komander, D., Thomas, C.C., Lizcano, J.M., Deak, M., Alessi, D.R., van Aalten, D.M. EMBO J. (2002) [Pubmed]
  11. Visualizing inducible nitric-oxide synthase in living cells with a heme-binding fluorescent inhibitor. Panda, K., Chawla-Sarkar, M., Santos, C., Koeck, T., Erzurum, S.C., Parkinson, J.F., Stuehr, D.J. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  12. Alleles at the PRH1 locus coding for the human salivary-acidic proline-rich proteins Pa, Db, and PIF. Azen, E.A., Kim, H.S., Goodman, P., Flynn, S., Maeda, N. Am. J. Hum. Genet. (1987) [Pubmed]
  13. Dermcidin is constitutively produced by eccrine sweat glands and is not induced in epidermal cells under inflammatory skin conditions. Rieg, S., Garbe, C., Sauer, B., Kalbacher, H., Schittek, B. Br. J. Dermatol. (2004) [Pubmed]
  14. A prospective randomized comparison of protracted infusional 5-fluorouracil with or without weekly bolus cisplatin in metastatic colorectal carcinoma. A Mid-Atlantic Oncology Program study. Lokich, J.J., Ahlgren, J.D., Cantrell, J., Heim, W.J., Wampler, G.L., Gullo, J.J., Fryer, J.G., Alt, D.E. Cancer (1991) [Pubmed]
  15. Effect of PGE1, PGI2, and PGF2 alpha analogs on collagen gel compaction in vitro and interstitial pressure in vivo. Berg, A., Ekwall, A.K., Rubin, K., Stjernschantz, J., Reed, R.K. Am. J. Physiol. (1998) [Pubmed]
  16. Identification of the human cDNA for new survival/evasion peptide (DSEP): studies in vitro and in vivo of overexpression by neural cells. Cunningham, T.J., Jing, H., Akerblom, I., Morgan, R., Fisher, T.S., Neveu, M. Exp. Neurol. (2002) [Pubmed]
  17. Excitotoxicity and mitochondria. Nicholls, D.G., Budd, S.L., Ward, M.W., Castilho, R.F. Biochem. Soc. Symp. (1999) [Pubmed]
  18. Detrusor contraction duration may predict response to alpha-blocker therapy for lower urinary tract symptoms. Kaplan, S.A., Stifelman, M., Avillo, C., Reis, R.B., Te, A.E. Eur. Urol. (2000) [Pubmed]
  19. Mitochondria and neuronal glutamate excitotoxicity. Nicholls, D.G., Budd, S.L. Biochim. Biophys. Acta (1998) [Pubmed]
  20. Is pulsatile perfusion necessary for renal transplantation engrafting kidneys from cardiac death donors? Kusaka, M., Kubota, Y., Sasaki, H., Maruyama, T., Hayakawa, K., Shiroki, R., Hoshinaga, K. Transplant. Proc. (2006) [Pubmed]
  21. Osteodystrophy of diabetics in chronic dialysis: a histomorphometric study. Aubia, J., Serrano, S., Mariñoso, L., Hojman, L., Diez, A., Lloveras, J., Masramon, J. Calcif. Tissue Int. (1988) [Pubmed]
  22. Molecular structure, infrared spectrum, and photochemistry of squaric Acid dimethyl ester in solid argon. Breda, S., Reva, I., Lapinski, L., Fausto, R. The journal of physical chemistry. A, Molecules, spectroscopy, kinetics, environment & general theory. (2006) [Pubmed]
  23. Clinical management of dialysis-related carnitine deficiency: three case studies. Lindberg, J., Sadler, R., Slowik, M. Nephrology news & issues. (2003) [Pubmed]
  24. Postsecretory processing generates multiple cathelicidins for enhanced topical antimicrobial defense. Murakami, M., Lopez-Garcia, B., Braff, M., Dorschner, R.A., Gallo, R.L. J. Immunol. (2004) [Pubmed]
  25. Validity of 18F-fluorodeoxyglucose imaging with a dual-head coincidence gamma camera for detection of myocardial viability. Hasegawa, S., Uehara, T., Yamaguchi, H., Fujino, K., Kusuoka, H., Hori, M., Nishimura, T. J. Nucl. Med. (1999) [Pubmed]
  26. Generation of multiple stable dermcidin-derived antimicrobial peptides in sweat of different body sites. Rieg, S., Seeber, S., Steffen, H., Humeny, A., Kalbacher, H., Stevanovic, S., Kimura, A., Garbe, C., Schittek, B. J. Invest. Dermatol. (2006) [Pubmed]
 
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