**Author details**

Mokhtar Arazpour University of Social Welfare and Rehabilitation Sciences, Tehran, Iran

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© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

*Introductory Chapter: Technology and Orthotics and Prosthetics DOI: http://dx.doi.org/10.5772/intechopen.97696*


**Animal Models of Angiogenesis and Lymphangiogenesis**

L. D. Jensen1,2 et al.\* *1Department of Microbiology, Tumor and Cell Biology, The Karolinska Institute, Stockholm, 2Institution of Medicine and Health, Linköping University, Linköping, Sweden*


**1. Introduction**

Bee venom is a unique weapon in the primordial animal kingdom in the defense of the colony. This poison is formed by a complex mixture of efficient proteins designed to protect bees against a wide variety of predators [1]. Bee venom is found in the abdominal cavity (inside a gland) and contains at least 18 active components that have a wide variety of pharmaceutical properties such as melittin, apamin, adolapin, mast cell degranulation peptide (MCD), enzymes (such as phospholipase), biologically active amines (histamine and epinephrine), and non-peptidic components [2]. Melittin is the main component in the venom of the western bee representing 50% of the total dry weight of the apitoxin [3, 4].

Melittin is synthesized in the form of a precursor called prepromelittin, which plays a crucial role in the attachment of the growing polypeptide chain to the membrane of the endoplasmic reticulum and its vectorial discharge into the lumen [5]. This is because it contains a signal peptide that could be removed by the enzyme signal peptidase on the luminal side of the endoplasmic reticulum (ER) [6], giving rise to a peptide called promelittin [7].

Prepromelittin was detected upon translation of melittin mRNA in cell-free systems [8], but it has not been found in any cellular system. Promelittin also

contains some polar amino acids more than melittin at the N-terminal end that are eliminated by a protease after translation [9]. These polar amino acids at this end ensure that this toxic peptide is never present during its translation into the ribosomes [10]. The main reason for this is that the N-terminal region of melittin is predominantly hydrophobic while the carboxy-terminal region is hydrophilic due to the presence of a stretch of positively charged amino acid [7], leading to an amphipath that allows it to interact with the biological membranes [11]. Melittin has diverse biological and pharmacological activities [12], in particular the ability to modify the functions of the immune system in the body [13]. It has been seen that the addition of melittin to bacteria increases the turgor pressure of the cells followed by a decrease in the cell pressure, which could destroy the cellular envelope and could be the reason for cell lysis and its antimicrobial properties [14]. In human erythrocytes, melittin binds rapidly to its membrane and forms pores leading to an alteration of the permeability that causes the release of hemoglobin to the extracellular medium, and this causes the hemolysis at room temperature [7]. It also has the capacity to affect the dynamics of membrane proteins, causing their aggregation and immobilizing them in the plane of the lipid bilayer [15] and acting as a potent inhibitor of Ca2+ ATPase, H+ K+ ATPase, Na+ K+ ATPase, and protein kinase (**Figure 1**) [7].

Recent experiments have shown beneficial effects in the application of this poison on human health acting as anti-mutagenic, anti-inflammatory, contraceptive, and radioprotectant against cancer [16–18]. Melittin causes the cancer cell death by apoptosis by activating caspases and matrix metalloproteinases [2]. In addition, melittin has a direct suppressive effect in the production of HIV-1 [19]. Due to the multiple therapeutic applications of this oligopeptide, it is desirable to

*Cloning and Identification System of* Apis mellifera *Melittin cDNA in* Escherichia coli *DOI: http://dx.doi.org/10.5772/intechopen.101520*

obtain melittin-producing bacteria for their large-scale production in biological reactors. The objective of this study has been precisely to transform *Escherichia coli* with western honey bee (*A. mellifera*) gene through a plasmidic vector as a first step for an industrial production.