Disease relevance of mastoparan

• The ability of mastoparan to stimulate mitogenesis was reduced by pertussis toxin treatment [1].
• The enzymatic activity of the PLD protein was activated within minutes after the onset of dehydration, and although it was not inducible by abscisic acid, PLD activity did increase in response to mastoparan, which suggests a role for heterotrimeric G proteins in PLD regulation [2].
• We find that activation of pertussis toxin-sensitive G-proteins by mastoparan increases neurite outgrowth from neuroblastoma cells [3].
• Both the GAP-43(1-10) peptide and the G-protein-activating peptide mastoparan induce growth cone collapse and inhibit neurite extension from embryonic chick dorsal root ganglion and retinal neurons [4].
• Mastoparan thus displays a novel mode of toxicity by acting directly on G proteins to mimic the role normally played by agonist-liganded receptors [5].

Psychiatry related information on mastoparan

• Binding was proportional to the concentration of GTP-gamma S and was concentration-dependently stimulated by mastoparan equivalently in control and Alzheimer's disease prefrontal cortical membranes [6].

High impact information on mastoparan

• In culture, growth cone collapse can be caused by solubilized embryonic brain membranes, central nervous system myelin, a 35-kilodalton protein isolated from myelin, and mastoparan [7].
• Mastoparan, which directly activates G-proteins (and insulin secretion from beta cells), also stimulated the carboxyl methylation of gamma subunits in intact HIT cells [8].
• Pertussis toxin treatment of the membranes appeared to increase the rate of vesicle formation, but did not prevent the membrane damage induced by mastoparan [9].
• We conclude that ARFp13 is not a specific inhibitor of ARF function, as originally proposed, and that surface active peptides, such as mastoparan, have the potential for introducing artifacts that complicate the analysis of trimeric G protein involvement in regulation of Golgi vesicle dynamics [9].
• Although coated pit invagination is resistant to GTP gamma S, A1F4-, and mastoparan, late events involved in coated vesicle budding are inhibited by these antagonists of G protein function [10].

Chemical compound and disease context of mastoparan

• This interaction is inhibited by the sialic acid-binding peptide mastoparan and by the synthetic fragments FGF-2(112-129) and, to a lesser extent, FGF-2(130-155), whereas peptides FGF-2(10-33), FGF-2(39-59), FGF-2(86-96), and the basic peptide HIV-1 Tat(41-60) were ineffective [11].
• Pertussis toxin, wortmannin, and a Ras farnesyltransferase inhibitor peptide blocked, whereas mastoparan mimicked, the CB(1) receptor-evoked activation of JNK, supporting the involvement of a G(i)/G(o)-protein, phosphoinositide 3'-kinase and Ras [12].
• A G protein inhibitor, N-ethylmaleimide (10(-3) mol/L), attenuated the response to mastoparan (10(-7) mol/L) (67 +/- 4% of control response), whereas pertussis toxin treatment did not [13].
• In contrast, in isolated cultured hepatocytes, mastoparan inhibited [3H] thymidine incorporation, while pertussis toxin and 8-bromo-cAMP were mitogenic [14].
• The heterotrimeric G-protein agonists mastoparan, Mas7, melittin, compound 48/80 and cholera toxin provoke root hair deformation, whereas the heterotrimeric G-protein antagonist pertussis toxin inhibits mastoparan and Nod factor NodNGR[S]- (from Rhizobiumsp. NGR234) induced root hair deformation [15].

Biological context of mastoparan

• The synergistic mitogenic stimulation by mastoparan can be dissociated from activation of phospholipase C. Mastoparan did not stimulate phosphoinositide breakdown, Ca2+ mobilization or protein kinase C-mediated phosphorylation of a major cellular substrate or transmodulation of the epidermal growth factor receptor [1].
• These results demonstrate, for the first time, that mastoparan stimulates reinitiation of DNA synthesis in Swiss 3T3 cells and indicate that this peptide may be a useful probe to elucidate signal transduction mechanisms in mitogenesis [1].
• Mastoparan stimulates exocytosis at a Ca(2+)-independent late site in stimulus-secretion coupling. Studies with the RINm5F beta-cell line [16].
• In the absence of mastoparan, the half-maximum inhibition of channel activity (IC50) occurred at 1.85 +/- 0.25 nM calmodulin at a cGMP concentration of 12.5 microM; in the presence of mastoparan, the IC50 value increased to 20.3 +/- 3.8 nM calmodulin [17].
• Selective regulation of apical endocytosis in polarized Madin-Darby canine kidney cells by mastoparan and cAMP [18].

Anatomical context of mastoparan

• Mastoparan is a cationic amphipathetic peptide that activates trimeric G proteins, and increases binding of the coat protein beta-COP to Golgi membranes [9].
• Basic secretagogues of mast cells, such as compound 48/80 and mastoparan, are capable of inducing secretion in a mechanism that bypasses PLC by directly activating a G-protein that is presumably located downstream from PLC (GE) [19].
• Mastoparan, a basic tetradecapeptide isolated from wasp venom, is a novel mitogen for Swiss 3T3 cells [1].
• In addition, 48/80, like mastoparan, is capable of directly stimulating the GTPase activity of G-proteins in a cell-free system [19].
• Furthermore, a flagellar excision-defective mutant, fa-1, did not shed its flagella in response to low pH or mastoparan, yet both of these agents activated phospholipase C in these cells [20].

Associations of mastoparan with other chemical compounds

• Addition of neomycin (an inhibitor of phospholipase C) before exposure of cells to low pH or mastoparan prevented the increase in inositol 1,4,5-trisphosphate and also prevented deflagellation [20].
• Pretreatment with glibenclamide alone reversed mastoparan dilation to constriction in small microvessels, whereas it only offset the dilation without producing constriction in large microvessels [21].
• Furthermore, while ethanol had no significant effect on basal mitogenesis in H4IIE cells or hepatocytes, increased mitogenesis caused by direct Gialpha-protein stimulation (mastoparan M7; 10-5,000 nmol/L) was further enhanced in the presence of ethanol, an effect that was completely blocked following Gi-protein inhibition (PTx; 100 ng/mL) [22].
• These changes were quantitatively similar to the percentage increases in 35S-labeled guanosine 5'-O-(thiotriphosphate) binding in membranes treated with equivalent concentrations of ZP or mastoparan (Ward et al., 1992) [23].
• Following cell membrane fractionation mastoparan specifically stimulated a high activity Golgi/endosomal pool of PI4KIIalpha independently of exogenous guanine nucleotides [24].

Gene context of mastoparan

• Mastoparan and mastoparan X, compounds which can activate phospholipase C and hence protein kinase C, also decreased beta/A4 peptide production in CHO cells stably transfected with APP695 [25].
• In contrast, HMEC activation by TLR2 agonists, TNF-alpha, or IL-1beta was insensitive to mastoparan [26].
• Unsaturated fatty acids and mastoparan increased phosphorylation of ABCA1 serines [27].
• Mastoparan, a G protein agonist peptide, differentially modulates TLR4- and TLR2-mediated signaling in human endothelial cells and murine macrophages [26].
• Confocal light microscopy revealed a substantial degree of colocalization of Rac (and, to a lesser degree, Cdc42) with insulin in beta-cells exposed to mastoparan [28].

Analytical, diagnostic and therapeutic context of mastoparan

• After deflagellation by low pH or mastoparan, a potent activator of G proteins, there was a rapid increase in levels of inositol 1,4,5-trisphosphate measured by use of receptor-binding assays and HPLC [20].
• However, D2N as the only peptide exhibiting specific effects did not exhibit the predicted amphipathic alpha-helix observed for mastoparan (Higashijima, T., Burnier, J., and Ross, E. M. (1990) J. Biol. Chem. 265, 14176-14186) as demonstrated by circular dichroism spectroscopy [29].
• Immunoprecipitation with Gi alpha subtype-specific antisera and subsequent autoradiography revealed that mastoparan activated Gi1, Gi2, and Gi3 in the membranes [23].
• Specific experiments including incubation with mastoparan or mas 7, GTP iontophoresis, and IP3 quantification strongly suggest that these receptors must be coupled with G-proteins to be functional [30].
• By gel filtration on a Fractogel TSK HW 50 column followed by cation-exchange chromatography on CM-Trisacryl M, a tetradecapeptide amide, designated 'mastoparan B', was purified from the venom of the hornet Vespa basalis [31].

References