“Melittin”的意思、由来-开放百科全书

The principal function of melittin as a component of bee venom is to cause pain and destruction of tissue of intruders that threaten bees hive. However in honey bees, melittin is not only expressed in the venom gland, but also in other tissues when infected with pathogens. The two venom molecules, melittin and secapin, are over-expressed in honey bees infected with various pathogens, possibly indicating a role for melittin in the immune response of bees to infectious diseases.^[3]

Structure

Melittin is a small peptide with no disulfide bridge; the N-terminal part of the molecule is predominantly hydrophobic and the C-terminal part is hydrophilic and strongly basic. In water, it forms a tetramer but it also can spontaneously integrate itself into cell membranes.^[4]

Mechanism of action

Injection of melittin into animals and humans causes pain sensation. It has strong surface effects on cell membranes causing pore-formation in epithelial cells and the destruction of red blood cells. Melittin also activates nociceptor (pain receptor) cells through a variety of mechanisms.^[2]

Melittin can open thermal nociceptor TRPV1 channels via cyclooxygenase metabolites resulting in depolarization of nociceptor cells. The pore forming effects in cells causes the release of pro-inflammatory cytokines. It also activates G-protein-coupled receptor-mediated opening of transient receptor potential channels. Finally melittin up-regulates the expression of Nav1.8 and Nav1.9 sodium channels in nociceptor cell causing long term action potential firing and pain sensation.^[2]

Melittin inhibits protein kinase C, Ca²⁺/calmodulin-dependent protein kinase II, myosin light chain kinase, and Na⁺/K⁺-ATPase (synaptosomal membrane). Mellitin blocks transport pumps such as the Na⁺-K⁺-ATPase and the H⁺-K⁺-ATPase. In vitro, melittin increases the permeability of cell membranes to ions,^[7] particularly Na⁺ and indirectly Ca²⁺, because of the Na⁺-Ca²⁺-exchange. This effect results in morphological and functional changes, particularly in excitable tissues.^[5]

Potential medical applications

Bee venom therapy has been used as a traditional medicine for the treatment of pain, inflammatory diseases, and of cancer.^[6] This has motivated research into the use of the main active component of bee venom, melittin, to treat these same diseases. However the non-specific toxicity of melittin has severely limited its clinical application.^[7] While melittin has been studied in in vitro and animal models for the treatment of inflammation^[8] and cancer,^[6]^[9] human efficacy data is lacking.

References

1. ^[https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=16129627 Melitten - Compound Summary], PubChem.
2. ^¹²{{cite journal | vauthors = Chen J, Guan SM, Sun W, Fu H | title = Melittin, the Major Pain-Producing Substance of Bee Venom | journal = Neuroscience Bulletin | volume = 32 | issue = 3 | pages = 265–72 | year = 2016 | pmid = 26983715 | pmc = 5563768 | doi = 10.1007/s12264-016-0024-y }}
3. ^{{cite journal | vauthors = Doublet V, Poeschl Y, Gogol-Döring A, Alaux C, Annoscia D, Aurori C, Barribeau SM, Bedoya-Reina OC, Brown MJ, Bull JC, Flenniken ML, Galbraith DA, Genersch E, Gisder S, Grosse I, Holt HL, Hultmark D, Lattorff HM, Le Conte Y, Manfredini F, McMahon DP, Moritz RF, Nazzi F, Niño EL, Nowick K, van Rij RP, Paxton RJ, Grozinger CM | display-authors = 6 | title = Unity in defence: honeybee workers exhibit conserved molecular responses to diverse pathogens | journal = BMC Genomics | volume = 18 | issue = 1 | pages = 207 | date = March 2017 | pmid = 28249569 | pmc = 5333379 | doi = 10.1186/s12864-017-3597-6 }}
4. ^{{cite journal | vauthors = Terwilliger TC, Eisenberg D | title = The structure of melittin. II. Interpretation of the structure | journal = The Journal of Biological Chemistry | volume = 257 | issue = 11 | pages = 6016–22 | year = 1982 | pmid = 7076662 | doi = | url = http://www.jbc.org/content/257/11/6016.full.pdf }}
5. ^¹{{cite journal | vauthors = Ma R, Mahadevappa R, Kwok HF | title = Venom-based peptide therapy: insights into anti-cancer mechanism | journal = Oncotarget | volume = 8 | issue = 59 | pages = 100908-100930 | date = November 2017 | pmid = 29246030 | pmc = 5725072 | doi = 10.18632/oncotarget.21740 | url = https://doi.org/10.18632/oncotarget.21740 }}
6. ^¹{{cite journal | vauthors = Rady I, Siddiqui IA, Rady M, Mukhtar H | title = Melittin, a major peptide component of bee venom, and its conjugates in cancer therapy | journal = Cancer Letters | volume = 402 | issue = | pages = 16–31 | year = 2017 | pmid = 28536009 | pmc = 5682937 | doi = 10.1016/j.canlet.2017.05.010 }}
7. ^{{cite journal | vauthors = Liu CC, Hao DJ, Zhang Q, An J, Zhao JJ, Chen B, Zhang LL, Yang H | title = Application of be venom and its main constituent melittin for cancer treatment | journal = Cancer Chemotherapy and Pharmacology | volume = 78 | issue = 6 | pages = 1113–1130 | year = 2016 | pmid = 27677623 | doi = 10.1007/s00280-016-3160-1 }}
8. ^{{cite journal | vauthors = Lee G, Bae H | title = Anti-Inflammatory Applications of Melittin, a Major Component of Bee Venom: Detailed Mechanism of Action and Adverse Effects | journal = Molecules (Basel, Switzerland) | volume = 21 | issue = 5 | pages = | year = 2016 | pmid = 27187328 | doi = 10.3390/molecules21050616 }}
9. ^{{cite journal | vauthors = Gajski G, Garaj-Vrhovac V | title = Melittin: a lytic peptide with anticancer properties | journal = Environmental Toxicology and Pharmacology | volume = 36 | issue = 2 | pages = 697–705 | year = 2013 | pmid = 23892471 | doi = 10.1016/j.etap.2013.06.009 }}

Function

Structure

Mechanism of action

Potential medical applications

References

External links