Phospholipase A2-A Significant Bio-Active Molecule in Honeybee (Apis mellifera L.) Venom

Abstract

Phospholipase A₂ (PLA₂) is a prevalent molecule in the honeybee venom. Its importance is reflected by the number of scientists focused on studying it from various points of view. This review summarises a significant amount of data concerning this fascinating substance. Firstly, the origin and occurrence of PLA₂, with similarities and differences among species or populations of bees are highlighted. Next, its synthesis, post-translational processing and structural features are described, followed by the PLA₂ availability. In a larger section, the multiple effects of honeybee venom PLA₂ are detailed, starting with the main ability as an enzyme to interact with biological membranes and to hydrolyse the sn-2 ester bond in 1,2-diacyl-sn-3-phosphoglycerides; the docking process, the substrate binding and the catalytic steps are analysed too. Then, the pro-/anti-inflammatory effect and allergenic property, the anticoagulant effect and the involvement of PLA₂ in apoptosis are revised. Selected antiviral, antibiotic and antitumoral effects of PLA₂, as well as its use in immunotherapy are mentioned as beneficial applications. Additionally, the mechanisms of toxicity of PLA₂ are presented in detail. Finally, a number of anti-PLA₂ compounds are enumerated. In each section, the features of the honeybee venom molecule are discussed in relation to PLA₂s from other species.

Keywords: Apis mellifera; allergen; anti-PLA2 molecules; cell membrane; honeybee venom; phospholipase A2; phospholipids; toxicity.

Figure 1

Primary, secondary and tertiary structures of the honeybee venom phospholipase A₂ (hvPLA₂) imagined based on the numerous structures available in [61]. See the text for the significance of numbers. Black lines, disulfide bonds; branched lines, glycosylation motif; grey circle, Ca²⁺-binding domain; pink circle, possible area of the catalytic site.

Figure 2

Venom collection device using the electric stimulation of bees. A.m.c., Apis mellifera carpatica; HBV, honeybee venom under a latex membrane; igcd, impulse generator of the collecting device; Zn e, zinc electrodes. (personal archive A.F.).

Figure 3

Main effects of the hvPLA₂.

Figure 4

Interaction of the hvPLA₂ with a biological membrane.

Figure 5

Severe ultrastructural alterations of orthodox mitochondria isolated from rat adrenocortical cells, generated in vitro by experimental administration of a high dose of hvPLA₂ (personal archive A.F.). cm, condensed mitochondrion; om, orthodox mitochondrion; tc, tubular cristae; vc, vesicular cristae (abnormal) (personal archive A.F.).

Figure 6

Severe ultrastructural alterations of Sertoli cells in a seminiferous tubule, generated in vivo by experimental administration of a high dose of hvPLA₂ in rats. bm, basement membrane; n, nucleus; sI, primary spermatocyte; sII, secondary spermatocyte; Se, Sertoli cell; sg, spermatogonia. (personal archive A.F.).