Abstract
The β-neurotoxic secreted phospholipases A2 (sPLA2s) block neuro-muscular transmission by poisoning nerve terminals. Damage inflicted by such sPLA2s (β-ntx) on neuronal mitochondria is characteristic, very similar to that induced by structurally homologous endogenous group IIA sPLA2 when its activity is elevated, as, for example, in the early phase of Alzheimer’s disease. Using ammodytoxin (Atx), the β-ntx from the venom of the nose-horned viper (Vipera a. ammodytes), the sPLA2 receptor R25 has been detected in neuronal mitochondria. This receptor has been purified from porcine cerebral cortex mitochondria by a new Atx-affinity-based chromatographic procedure. Mass spectrometry analysis revealed R25 to be the subunit II of cytochrome c oxidase (CCOX), an essential constituent of the respiratory chain complex. CCOX was confirmed as being the first intracellular membrane receptor for sPLA2 by alternative Atx-affinity-labellings of purified CCOX, supported also by the encounter of Atx and CCOX in PC12 cells. This discovery suggests the explanation of the mechanism by which β-ntx hinders production of ATP in poisoned nerve endings. It also provides a new insight into the potential function and dysfunction of endogenous GIIA sPLA2 in mitochondria.
Highlights
Understanding the mechanism of the presynaptic neurotoxicity (β-neurotoxicity) exerted by phospholipases A2 secreted by some Elapidae and Viperidae snake venoms has presented a major challenge for several decades
The Atx-binding activity of R25 was unaffected by washing the membranes with 1 M NaCl8, so they were washed in this way to remove contaminating proteins as much as possible
This was shown to be the lowest concentration of the detergent still providing optimal extraction of the receptor[8]
Summary
Understanding the mechanism of the presynaptic neurotoxicity (β-neurotoxicity) exerted by phospholipases A2 (sPLA2s) secreted by some Elapidae and Viperidae snake venoms has presented a major challenge for several decades. These toxins belong mostly to group I or II (GI or GII) sPLA2s1. Supported by the discovery of a high-affinity membrane receptor for Atx in mitochondria of the porcine cerebral cortex, R257,8, this organelle is clearly a very important target of β-neurotoxic sPLA2s in neuronal cells. As an important breakthrough in this direction we report here the solution of the almost two-decade-old enigma of the molecular identity of R25, the mitochondrial receptor for Atx, the snake venom GIIA sPLA2
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
