Kunitz-Type Peptides from the Sea Anemone Heteractis crispa Demonstrate Potassium Channel Blocking and Anti-Inflammatory Activities

Peigneur, Steve; Sintsova, Oksana; Pinheiro-Júnior, Ernesto Lopes; Климович, А. А.; Menshov, Alexander S.; Kalinovsky, Anatoly I.; Isaeva, Marina; Monastyrnaya, Margarita; Kozlovskaya, É. P.; Tytgat, Jan; Leychenko, Elena

doi:10.3390/biomedicines8110473

Cited by 21 publications

(23 citation statements)

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“…Sea anemone Kunitz-type peptides can block Kv channels [ 60 ], which are known to be actively involved in the regulation of neuronal processes and considered as potential therapeutic targets for Parkinson’s disease [ 61 , 62 ]. Earlier we reported that HCRG1 and HCRG2 block several Kv1.x isoforms (Kv1.1, Kv1.2, Kv1.3, Kv1.6) in nM range [ 31 ], and now they showed full suppression of ROS formation in 6-OHDA-treated cells, but these peptides did not affect cell viability. They probably will be active in vivo similar to Kunitz-type toxin PcKuz3 of P. caribaeorum showing neuroprotective activity on 6-OHDA treated zebrafish Danio rerio [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, for some of them, cellular targets have already been found that allow explaining their biological effects. It has been found that TRPV1 is the target of APHC1-3 (partial inhibition up to 50%) and HCRG21 (full inhibition) resulting in analgesic and anti-inflammatory effect in mice [ 10 , 12 , 29 , 30 ], whereas Kv channels are the targets of HCRG1 and HCRG2 that block them and demonstrate anti-inflammatory activity reducing expression level of TNF-α, IL-6, and proIL-1β in macrophages [ 14 ], as well as suppressing TNF-α production in acute carrageenan-induced edema model [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

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Sea Anemone Kunitz-Type Peptides Demonstrate Neuroprotective Activity in the 6-Hydroxydopamine Induced Neurotoxicity Model

et al. 2021

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Kunitz-type peptides from venomous animals have been known to inhibit different proteinases and also to modulate ion channels and receptors, demonstrating analgesic, anti-inflammatory, anti-histamine and many other biological activities. At present, there is evidence of their neuroprotective effects. We have studied eight Kunitz-type peptides of the sea anemone Heteractis crispa to find molecules with cytoprotective activity in the 6-OHDA-induced neurotoxicity model on neuroblastoma Neuro-2a cells. It has been shown that only five peptides significantly increase the viability of neuronal cells treated with 6-OHDA. The TRPV1 channel blocker, HCRG21, has revealed the neuroprotective effect that could be indirect evidence of TRPV1 involvement in the disorders associated with neurodegeneration. The pre-incubation of Neuro-2a cells with HCRG21 followed by 6-OHDA treatment has resulted in a prominent reduction in ROS production compared the untreated cells. It is possible that the observed effect is due to the ability of the peptide act as an efficient free-radical scavenger. One more leader peptide, InhVJ, has shown a neuroprotective activity and has been studied at concentrations of 0.01-10.0 µM. The target of InhVJ is still unknown, but it was the best of all eight homologous peptides in an absolute cell viability increment on 38% of the control in the 6-OHDA-induced neurotoxicity model. The targets of the other three active peptides remain unknown.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sea Anemone Kunitz-Type Peptides Demonstrate Neuroprotective Activity in the 6-Hydroxydopamine Induced Neurotoxicity Model

et al. 2021

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“…They also demonstrate that, by simply introducing one additional residue, the toxin is converted from a Na V 1.7 activator into an inhibitor, which can be crucial for designing effective analgesic leads. Novel toxins with potential anti-inflammatory activity are further reported from the venom of a sea anemone [ 68 ]. In addition to their proposed medical applications, venom components are also useful tools for research.…”

Section: Contributions To This Special Issuementioning

confidence: 99%

Animal Venoms—Curse or Cure?

Herzig

2021

Biomedicines

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An estimated 15% of animals are venomous, with representatives spread across the majority of animal lineages. Animals use venoms for various purposes, such as prey capture and predator deterrence. Humans have always been fascinated by venomous animals in a Janus-faced way. On the one hand, humans have a deeply rooted fear of venomous animals. This is boosted by their largely negative image in public media and the fact that snakes alone cause an annual global death toll in the hundreds of thousands, with even more people being left disabled or disfigured. Consequently, snake envenomation has recently been reclassified by the World Health Organization as a neglected tropical disease. On the other hand, there has been a growth in recent decades in the global scene of enthusiasts keeping venomous snakes, spiders, scorpions, and centipedes in captivity as pets. Recent scientific research has focussed on utilising animal venoms and toxins for the benefit of humanity in the form of molecular research tools, novel diagnostics and therapeutics, biopesticides, or anti-parasitic treatments. Continued research into developing efficient and safe antivenoms and promising discoveries of beneficial effects of animal toxins is further tipping the scales in favour of the “cure” rather than the “curse” prospect of venoms.

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“…The HCRG21 fold correctness was assessed using NMR spectroscopy on a Bruker Avance III 700 MHz spectrometer (Bruker Biospin, San Jose, CA, USA) equipped with a triple resonance z-gradient TXO probe, as described previously [16].…”

Section: Production Of Recombinant Peptidementioning

confidence: 99%

“…This procedure was conducted as we described in a previous article [16]. The animals were terminally anaesthetized with sodium pentobarbital (40 mg per mouse i.p., Euthatal, Merial Animal Health, Essex, UK) 24 h after carrageenan injection.…”

Section: Animals Euthanasia Procedures and Blood Samplingmentioning

confidence: 99%

TRPV1 Blocker HCRG21 Suppresses TNF-α Production and Prevents the Development of Edema and Hypersensitivity in Carrageenan-Induced Acute Local Inflammation

et al. 2021

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Currently the TRPV1 (transient receptor potential vanilloid type 1) channel is considered to be one of the main targets for pro-inflammatory mediators including TNF-α. Similarly, the inhibition of TRPV1 activity in the peripheral nervous system affects pro-inflammatory mediator production and enhances analgesia in total. In this study, the analgesic and anti-inflammatory effects of HCRG21, the first peptide blocker of TRPV1, were demonstrated in a mice model of carrageenan-induced paw edema. HCRG21 in doses of 0.1 and 1 mg/kg inhibited edema formation compared to the control, demonstrated complete edema disappearance in 24 h in a dose of 1 mg/kg, and effectively reduced the productionof TNF-α in both doses examined. ELISA analysis of blood taken 24 h after carrageenan administration showed a dramatic cytokine value decrease to 25 pg/mL by HCRG21 versus 100 pg/mL in the negative control group, which was less than the TNF-α level in the intact group (40 pg/mL). The HCRG21 demonstrated potent analgesic effects on the models of mechanical and thermal hyperalgesia in carrageenan-induced paw edema. The HCRG21 relief effect was comparable to that of indomethacin taken orally in a dose of 5 mg/kg, but was superior to this nonsteroidal anti-inflammatory drug (NSAID) in duration (which lasted 24 h) in the mechanical sensitivity experiment. The results confirm the existence of a close relationship between TRPV1 activity and TNF-α production once again, and prove the superior pharmacological potential of TRPV1 blockers and the HCRG21 peptide in particular.

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Kunitz-Type Peptides from the Sea Anemone Heteractis crispa Demonstrate Potassium Channel Blocking and Anti-Inflammatory Activities

Cited by 21 publications

References 70 publications

Sea Anemone Kunitz-Type Peptides Demonstrate Neuroprotective Activity in the 6-Hydroxydopamine Induced Neurotoxicity Model

Sea Anemone Kunitz-Type Peptides Demonstrate Neuroprotective Activity in the 6-Hydroxydopamine Induced Neurotoxicity Model

Animal Venoms—Curse or Cure?

TRPV1 Blocker HCRG21 Suppresses TNF-α Production and Prevents the Development of Edema and Hypersensitivity in Carrageenan-Induced Acute Local Inflammation

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