Membrane-modifying properties of crotamine, a small peptide-toxin from Crotalus durissus terifficus venom

Sieber, Michaela; Bosch, Bettina; Hanke, Wolfgang; Lima, Vera Maura Fernandes de

doi:10.1016/j.bbagen.2013.10.031

Cited by 14 publications

(14 citation statements)

References 21 publications

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“…The surface potential (calculated from electrophoresis) at agglutination (~-5 mV) continued to rise far above the zero point to a high positive value (~+28 mV), surprising the experimenters [ 129 ]. These results fit our own results about the polylysine crotamine interaction with lipid monolayers and bilayers and the intact retina basement membrane [ 130 , 131 ] in which the peptide slowed metabolism and induced endocytosys. The polyarginine protamine had a very different physico-chemical interaction.…”

Section: Discussionsupporting

confidence: 91%

Relevance of Excitable Media Theory and Retinal Spreading Depression Experiments in Preclinical Pharmacological Research

Lima

Hanke

2014

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In preclinical neuropharmacological research, molecular, cell-based, and systems using animals are well established. On the tissue level the situation is less comfortable, although during the last decades some effort went into establishing such systems, i.e. using slices of the vertebrate brain together with optical and electrophysiological techniques. However, these methods are neither fast, nor can they be automated or upscaled. By contrast, the chicken retina can be used as a suitable model. It is easy accessible and can be kept alive in vitro for hours up to days. Due to its structure, in addition the retina displays remarkable intrinsic optical signals, which can be easily used in experiments. Also to electrophysiological methods the retina is well accessible. In excitable tissue, to which the brain and the retina belong, propagating excitation waves can be expected, and the spreading depression is such a phenomenon. It has been first observed in the forties of the last century. Later, Martins-Ferreira established it in the chicken retina (retinal spreading depression or RSD). The electrophysiological characteristics of it are identical with those of the cortical SD. The metabolic differences are known and can be taken into account. The experimental advantage of the RSD compared to the cortical SD is the pronounced intrinsic optical signal (IOS) associated with the travelling wave. This is due to the maximum transparency of retinal tissue in the functional state; thus any physiological event will change it markedly and therefore can be easily seen even by naked eye. The theory can explain wave spread in one (action potentials), two (RSDs) and three dimensions (one heart beat). In this review we present the experimental and the excitable media context for the data interpretation using as example the cholinergic pharmacology in relation to functional syndromes. We also discuss the intrinsic optical signal and how to use it in pre-clinical research.

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Section: Discussionsupporting

confidence: 91%

Relevance of Excitable Media Theory and Retinal Spreading Depression Experiments in Preclinical Pharmacological Research

Lima

Hanke

2014

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“…This toxin is structurally similar to human β-defensins, which, among other functions, exert an antibiotic effect through their ability to form pores in the bacterial membrane. For the above-mentioned reasons, crotamine has been categorized in the family of antimicrobial peptides (AMPs) (43)(44)(45)(46) .…”

Section: Resultsmentioning

confidence: 99%

EVALUATION OF THE ANTIBACTERIAL ACTIVITY OF Crotalus durissus terrificus CRUDE VENOM

et al. 2018

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Snake venoms are recognized as a promising source of pharmacologically active substances and are potentially useful for the development of new antimicrobial drugs. This study aimed to investigate the antimicrobial activity of the venom from the rattlesnake Crotalus durissus terrificus against several bacteria. Antibacterial activity was determined by using the plate microdilution method and the activity on the bacterial envelope structure was screened by using the crystal violet assay. The proteins in crude venom were separated by electrophoresis and characterized regarding their proteolytic activity. C. d. terrificus venom exhibited antimicrobial action against gram-positive and gram-negative bacteria. MIC values were defined for Pseudomonas aeruginosa ATCC 27853 (62.5 µg/mL), Staphylococcus aureus ATCC 25923 (125 µg/mL), and Micrococcus luteus ATCC 9341 (≤500 µg/mL). For Salmonella enterica serovar typhimurium ATCC 14028 and Corynebacterium glutamicum ATCC 13032, the decrease in bacterial growth was not detected visually, but was statistically significant. The crystal violet assay demonstrated that the crude venom increased bacterial cell permeability and the secreted protein profile agreed with previous reports. The results suggest that the proteins with lytic activity against bacteria in C. d. terrificus venom deserve further characterization as they may offer reinforcements to the weak therapeutic arsenal used to fight microbial multidrug resistance.

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“…The pharmacological properties of crotamine on different biological models include its analgesic potential [16], insulin release potential [11], memory persistence enhancement without psychomotor alterations [44] and antimicrobial and antiparasitic actions in several species [5,12,13,14,15,23]. Moreover, due to its cell-penetrating capacity and site-specific interactions, crotamine has been studied as a drug-mediating peptide and as a model for the discovery of new antitumor molecules [10,17,19,21,22,23].…”

Section: Discussionmentioning

confidence: 99%

“…Its three-dimensional structure αβ1β2β3 is similar to that of other human proteins intrinsically related to antimicrobial activity, such as β-defensins. Furthermore, positively charged regions distributed throughout the structure and a small area of negative charge optimize electrostatic interactions between crotamine and diverse cell membranes [1,2,3,4,5].…”

Section: Introductionmentioning

confidence: 99%

Intradermal Application of Crotamine Induces Inflammatory and Immunological Changes In Vivo

Silvestrini

Macedo

Andrade

et al. 2019

Toxins

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Crotamine is a single-chain polypeptide with cell-penetrating properties, which is considered a promising molecule for clinical use. Nevertheless, its biosafety data are still scarce. Herein, we assessed the in vivo proinflammatory properties of crotamine, including its local effect and systemic serum parameters. Sixty male Wistar rats were intradermically injected with 200, 400 and 800 µg crotamine and analyzed after 1, 3 and 7 days. Local effect of crotamine was assessed by determination of MPO and NAG activities, NO levels and angiogenesis. Systemic inflammatory response was assessed by determination of IL-10, TNF-α, CRP, NO, TBARS and SH groups. Crotamine induced macrophages and neutrophils chemotaxis as evidenced by the upregulation of both NAG (0.5–0.6 OD/mg) and MPO (0.1–0.2 OD/mg) activities, on the first and third day of analysis, respectively. High levels of NO were observed for all concentrations and time-points. Moreover, 800 μg crotamine resulted in serum NO (64.7 μM) and local tissue NO (58.5 μM) levels higher or equivalent to those recorded for their respective histamine controls (55.7 μM and 59.0 μM). Crotamine also induced a significant angiogenic response compared to histamine. Systemically, crotamine induced a progressive increase in serum CRP levels up to the third day of analysis (22.4–45.8 mg/mL), which was significantly greater than control values. Crotamine (400 μg) also caused an increase in serum TNF-α, in the first day of analysis (1095.4 pg/mL), however a significant increase in IL-10 (122.2 pg/mL) was also recorded for the same time-point, suggesting the induction of an anti-inflammatory effect. Finally, crotamine changed the systemic redox state by inducing gradual increase in serum levels of TBARS (1.0–1.8 μM/mL) and decrease in SH levels (124.7–19.5 μM/mL) throughout the experimental period of analysis. In summary, rats intradermally injected with crotamine presented local and systemic acute inflammatory responses similarly to histamine, which limits crotamine therapeutic use on its original form.

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Membrane-modifying properties of crotamine, a small peptide-toxin from Crotalus durissus terifficus venom

Cited by 14 publications

References 21 publications

Relevance of Excitable Media Theory and Retinal Spreading Depression Experiments in Preclinical Pharmacological Research

Relevance of Excitable Media Theory and Retinal Spreading Depression Experiments in Preclinical Pharmacological Research

EVALUATION OF THE ANTIBACTERIAL ACTIVITY OF Crotalus durissus terrificus CRUDE VENOM

Intradermal Application of Crotamine Induces Inflammatory and Immunological Changes In Vivo

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