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Chemical Compound Review

AC1L19JP     2-acetamido-N-[4,5-dihydroxy- 6...

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Disease relevance of MSH

  • A combinatorial chemistry-based diffusion assay is used to find random tripeptides that antagonize normal frog and human melanoma MSH receptors and to identify pharmacological groups responsible for receptor interaction [1].
  • Our finding that the human immunodeficiency virus, among several viruses, induces ACTH and MSH production in H9 T-lymphoma cells suggests an important role of these neuropeptides in the immunosuppression characteristic of such infections [2].
  • The substrate-induced conformational change of Mycobacterium tuberculosis mycothiol synthase [3].
  • Mycothiol (1-D-myo-inosityl 2-(N-acetyl-L-cysteinyl)amido-2-deoxy-alpha-D-glucopyranoside, MSH or AcCys-GlcN-inositol (Ins)) is the major reducing agent in actinomycetes, including Mycobacterium tuberculosis [4].
  • Data mining of the Corynebacterium glutamicum genome identified 4 genes analogous to the mshA, mshB, mshC, and mshD genes that are involved in biosynthesis of mycothiol in Mycobacterium tuberculosis and Mycobacterium smegmatis [5].

Psychiatry related information on MSH


High impact information on MSH

  • Because expression of, for example, the MC1 receptor is stimulated in a similar dose-dependent manner by UVR, cytokines, MSH peptides or melanin precursors, actions of the ligand peptides represent a stochastic (predictable) nonspecific response to environmental/endogenous stresses [10].
  • Identification of a widely distributed receptor for ACTH/MSH peptides, the melanocortin-5 receptor (MC5-R), suggested non-steroidally mediated systemic effects of these peptides [11].
  • We have identified a human homolog of the bacterial MutS and S. cerevisiae MSH proteins, called hMSH2 [12].
  • This sequence confirmed the known structure of the carboxyl half of POMC and revealed the presence of a new MSH-like moiety, gamma-MSH, within the 16,000-MW amino half of the precursor (16K fragment) [13].
  • 3) Recent evidence shows that neural elements in the VMN-DMN complex tonically restrain the orexigenic signals during the intermeal interval; the restraint is greatly aided by leptin's action via diminution of orexigenic (NPY) and augmentation of anorexigenic (GLP-1, alpha MSH, and CART) signals [14].

Chemical compound and disease context of MSH


Biological context of MSH


Anatomical context of MSH

  • High levels of MC5-R was found in multiple exocrine tissues, including Harderian, preputial, lacrimal, and sebaceous glands, and was also shown to be required for production and stress-regulated synthesis of porphyrins by the Harderian gland and ACTH/MSH-regulated protein secretion by the lacrimal gland [11].
  • Proopiomelanocortin (POMC), the precursor for melanotropic, corticotropic, and opioid peptides such as alpha-melanocyte-stimulating hormone (alpha MSH), ACTH, and other related peptides, was originally identified as a product of the pituitary gland [22].
  • These data provide first evidence that human keratinocytes produce POMC-derived peptides such as alpha MSH and ACTH [22].
  • Supernatants of human normal keratinocytes and an epidermal carcinoma cell line (A431) contained significant levels of immunoreactive alpha MSH and ACTH [22].
  • These data indicate that alpha- and beta MSH possess steroidogenic or growth-promoting properties, or both, for the fetal adrenal gland [23].

Associations of MSH with other chemical compounds

  • TPA and retinoic acid generally down-regulated MSH receptors but had no effect on HBL cells [20].
  • These genes encode several sigma factors, oxidative defence proteins, chaperones, systems to provide osmolytes, cysteine, mycothiol, and gas vesicle. sigma(B) controlled induction of itself and its two paralogues (sigma(L) and sigma(M)) in a hierarchical order of sigma(B)-->sigma(L)-->sigma(M), as revealed by S1 mapping and Western blot analyses [24].
  • Plasma alpha MSH IR decreased progressively from severe preterm to fullterm neonates born by vaginal delivery (VD; P < 0.001) or cesarean section (CS) with and without prenatal distress (P < or = 0.001 in both cases). alpha MSH IR was due, in all studied conditions, to three major forms: desacetyl alpha MSH, alpha MSH, and diacetyl alpha MSH [25].
  • (which use mycothiol, an inositol-containing thiol, as an intracellular redox reagent and have characteristic phosphatidylinositol-linked surface oligosaccharides) [26].
  • Action potentials in gland cells of rat pituitary pars intermedia: inhibition by dopamine, an inhibitor of MSH secretion [27].

Gene context of MSH

  • This work revealed a high-specificity binding state of MSH proteins for mismatch DNA that was not observed in bulk assays and allowed us to measure the affinity of MSH2-MSH6 for mismatch DNA as well as its footprint on DNA surrounding the mismatch site [28].
  • Corticotropin (ACTH) and melanotropin (MSH) peptides (melanocortins) are produced not only in the pituitary but also in the brain, with highest concentrations in the arcuate nucleus of the hypothalamus and the commisural nucleus of the solitary tract [29].
  • The hMSH2 (MSH for MutS homologue) protein forms a complex with a 160 kDa protein, and this heterodimer, hMutSalpha, has high affinity for a G/T mismatch [9,10] [30].
  • Together, MC3-R and/or MC-4R mRNA are found in every nucleus reported to bind MSH in the adult rat brain and define neuronal circuitry known to be involved in the control of diverse neuroendocrine and autonomic functions [31].
  • In conclusion, alpha MSH antagonizes CRH inhibition of LH secretion [32].

Analytical, diagnostic and therapeutic context of MSH


  1. Combinatorial diffusion assay used to identify topically active melanocyte-stimulating hormone receptor antagonists. Quillan, J.M., Jayawickreme, C.K., Lerner, M.R. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  2. Immunosuppressive effects of corticotropin and melanotropin and their possible significance in human immunodeficiency virus infection. Smith, E.M., Hughes, T.K., Hashemi, F., Stefano, G.B. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  3. The substrate-induced conformational change of Mycobacterium tuberculosis mycothiol synthase. Vetting, M.W., Yu, M., Rendle, P.M., Blanchard, J.S. J. Biol. Chem. (2006) [Pubmed]
  4. The crystal structure of 1-D-myo-inosityl 2-acetamido-2-deoxy-alpha-D-glucopyranoside deacetylase (MshB) from Mycobacterium tuberculosis reveals a zinc hydrolase with a lactate dehydrogenase fold. Maynes, J.T., Garen, C., Cherney, M.M., Newton, G., Arad, D., Av-Gay, Y., Fahey, R.C., James, M.N. J. Biol. Chem. (2003) [Pubmed]
  5. The Gene ncgl2918 Encodes a Novel Maleylpyruvate Isomerase That Needs Mycothiol as Cofactor and Links Mycothiol Biosynthesis and Gentisate Assimilation in Corynebacterium glutamicum. Feng, J., Che, Y., Milse, J., Yin, Y.J., Liu, L., Rückert, C., Shen, X.H., Qi, S.W., Kalinowski, J., Liu, S.J. J. Biol. Chem. (2006) [Pubmed]
  6. Peripherally administered [Nle4,D-Phe7]-alpha-melanocyte stimulating hormone increases resting metabolic rate, while peripheral agouti-related protein has no effect, in wild type C57BL/6 and ob/ob mice. Hoggard, N., Rayner, D.V., Johnston, S.L., Speakman, J.R. J. Mol. Endocrinol. (2004) [Pubmed]
  7. Neuroleptic-induced akathisia: a role for MSH peptides. Sandyk, R. Psychopharmacology (Berl.) (1989) [Pubmed]
  8. The MSH/ACTH(4-9) analog Org2766 counteracts isolation-induced enhanced social behavior via the amygdala. Hol, T., Spruijt, B.M. Peptides (1992) [Pubmed]
  9. The MSH/ACTH analog ORG 2766 in anxiety disorders. Den Boer, J.A., Westenberg, H.G., De Vries, H. Peptides (1992) [Pubmed]
  10. Corticotropin releasing hormone and proopiomelanocortin involvement in the cutaneous response to stress. Slominski, A., Wortsman, J., Luger, T., Paus, R., Solomon, S. Physiol. Rev. (2000) [Pubmed]
  11. Exocrine gland dysfunction in MC5-R-deficient mice: evidence for coordinated regulation of exocrine gland function by melanocortin peptides. Chen, W., Kelly, M.A., Opitz-Araya, X., Thomas, R.E., Low, M.J., Cone, R.D. Cell (1997) [Pubmed]
  12. The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Fishel, R., Lescoe, M.K., Rao, M.R., Copeland, N.G., Jenkins, N.A., Garber, J., Kane, M., Kolodner, R. Cell (1993) [Pubmed]
  13. Most of the coding region of rat ACTH beta--LPH precursor gene lacks intervening sequences. Drouin, J., Goodman, H.M. Nature (1980) [Pubmed]
  14. Interacting appetite-regulating pathways in the hypothalamic regulation of body weight. Kalra, S.P., Dube, M.G., Pu, S., Xu, B., Horvath, T.L., Kalra, P.S. Endocr. Rev. (1999) [Pubmed]
  15. Mycothiol biosynthesis and metabolism. Cellular levels of potential intermediates in the biosynthesis and degradation of mycothiol in mycobacterium smegmatis. Anderberg, S.J., Newton, G.L., Fahey, R.C. J. Biol. Chem. (1998) [Pubmed]
  16. Biochemistry of the initial steps of mycothiol biosynthesis. Newton, G.L., Ta, P., Bzymek, K.P., Fahey, R.C. J. Biol. Chem. (2006) [Pubmed]
  17. Characterization of Mycobacterium tuberculosis mycothiol S-conjugate amidase. Steffek, M., Newton, G.L., Av-Gay, Y., Fahey, R.C. Biochemistry (2003) [Pubmed]
  18. Plasma immunoreactive proopiomelanocortin peptides and cortisol in normal dogs and dogs with Addison's disease and Cushing's syndrome: basal concentrations. Peterson, M.E., Orth, D.N., Halmi, N.S., Zielinski, A.C., Davis, D.R., Chavez, F.T., Drucker, W.D. Endocrinology (1986) [Pubmed]
  19. Melanotropin receptors of murine melanoma characterized in cultured cells and demonstrated in experimental tumors in situ. Tatro, J.B., Entwistle, M.L., Lester, B.R., Reichlin, S. Cancer Res. (1990) [Pubmed]
  20. Homologous and heterologous regulation of alpha-melanocyte-stimulating hormone receptors in human and mouse melanoma cell lines. Siegrist, W., Stutz, S., Eberle, A.N. Cancer Res. (1994) [Pubmed]
  21. Beneficial effect of Org 2766 in treatment of peripheral neuropathy in streptozocin-induced diabetic rats. Van der Zee, C.E., Van der Hoop, R.G., Gispen, W.H. Diabetes (1989) [Pubmed]
  22. Proopiomelanocortin-derived peptides are synthesized and released by human keratinocytes. Schauer, E., Trautinger, F., Köck, A., Schwarz, A., Bhardwaj, R., Simon, M., Ansel, J.C., Schwarz, T., Luger, T.A. J. Clin. Invest. (1994) [Pubmed]
  23. Effects of melanotropic peptides on fetal adrenal gland. Rudman, D., Hollins, B.M., Lewis, N.C., Chawla, R.K. J. Clin. Invest. (1980) [Pubmed]
  24. A master regulator sigmaB governs osmotic and oxidative response as well as differentiation via a network of sigma factors in Streptomyces coelicolor. Lee, E.J., Karoonuthaisiri, N., Kim, H.S., Park, J.H., Cha, C.J., Kao, C.M., Roe, J.H. Mol. Microbiol. (2005) [Pubmed]
  25. alpha-Melanocyte-stimulating hormone during human perinatal life. Mauri, A., Volpe, A., Martellotta, M.C., Barra, V., Piu, U., Angioni, G., Angioni, S., Argiolas, A. J. Clin. Endocrinol. Metab. (1993) [Pubmed]
  26. Evolution of the diverse biological roles of inositols. Michell, R.H. Biochem. Soc. Symp. (2007) [Pubmed]
  27. Action potentials in gland cells of rat pituitary pars intermedia: inhibition by dopamine, an inhibitor of MSH secretion. Douglas, W.W., Taraskevich, P.S. J. Physiol. (Lond.) (1978) [Pubmed]
  28. Detection of high-affinity and sliding clamp modes for MSH2-MSH6 by single-molecule unzipping force analysis. Jiang, J., Bai, L., Surtees, J.A., Gemici, Z., Wang, M.D., Alani, E. Mol. Cell (2005) [Pubmed]
  29. Identification of a receptor for gamma melanotropin and other proopiomelanocortin peptides in the hypothalamus and limbic system. Roselli-Rehfuss, L., Mountjoy, K.G., Robbins, L.S., Mortrud, M.T., Low, M.J., Tatro, J.B., Entwistle, M.L., Simerly, R.B., Cone, R.D. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  30. Binding of insertion/deletion DNA mismatches by the heterodimer of yeast mismatch repair proteins MSH2 and MSH3. Habraken, Y., Sung, P., Prakash, L., Prakash, S. Curr. Biol. (1996) [Pubmed]
  31. Localization of the melanocortin-4 receptor (MC4-R) in neuroendocrine and autonomic control circuits in the brain. Mountjoy, K.G., Mortrud, M.T., Low, M.J., Simerly, R.B., Cone, R.D. Mol. Endocrinol. (1994) [Pubmed]
  32. Alpha-melanocyte-stimulating hormone antagonizes the inhibitory effect of corticotropin-releasing hormone on luteinizing hormone secretion during the luteal phase in normal women. Limone, P., Scipioni, T., Calvelli, P., Scaglione, E., Barberis, A.M., Dentelli, P., Isaia, G.C., Molinatti, G.M. J. Clin. Endocrinol. Metab. (1994) [Pubmed]
  33. Selective loss of alpha-melanotropin-amidating activity in primary cultures of rat intermediate pituitary cells. Eipper, B.A., Glembotski, C.C., Mains, R.E. J. Biol. Chem. (1983) [Pubmed]
  34. Alpha-melanocyte-stimulating hormone regulation of tyrosinase in Cloudman S-91 mouse melanoma cell cultures. Fuller, B.B., Lunsford, J.B., Iman, D.S. J. Biol. Chem. (1987) [Pubmed]
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