β-micrustoxin (Mlx-9), a PLA from snake venom: biochemical characterization and anti-proliferative effect mediated by p53.

Background: Endogenous phospholipases A (PLA) play a fundamental role in inflammation, neurodegenerative diseases, apoptosis and cellular senescence. Neurotoxins with PLA activity are found in snake venoms from the Elapidae and Viperidae families. The mechanism of action of these neurotoxins have been studied using hippocampal and cerebellar neuronal cultures showing [Ca]i increase, mitochondrial depolarization and cell death.

Snake Venom and a Phospholipase A Isolated from This Venom Elicit Macrophages to Form Lipid Droplets and Synthesize Inflammatory Lipid Mediators.

Viper snake (Cdr) is a subspecies found in northern area of Brazil. Among the snakes of genus subspecies, the venom of Cdr presents highest level of crotoxin, which is the major component of snake venoms, formed by two subunits (crotapotin and a phospholipase A named CBr) and presents potent neurotoxic activity. Curiously, the venom of (CdrV) is better neutralized by antibothropic than by anticrotalic serum, strongly suggesting that this venom has similarities with venom of genus snakes with regard to the ability to induce inflammation.

A Secreted Phospholipase A Induces Formation of Smooth Muscle Foam Cells Which Transdifferentiate to Macrophage-Like State.

Vascular smooth muscle cells (VSMCs) loaded with lipid droplets (LDs) are markers of atherosclerosis. In this disease, inflammatory Group IIA-secreted phospholipase As (GIIA sPLAs) are highly expressed in VSMCs, but their actions in these cells are unknown. Here, we investigated the ability of myotoxin III (MT-III), an ophidian GIIA sPLA sharing structural and functional features with mammalian GIIA sPLAs, to induce LD formation and lipid metabolism factors involved in this effect.

A Snake Venom-Secreted Phospholipase A Induces Foam Cell Formation Depending on the Activation of Factors Involved in Lipid Homeostasis.

MT-III, a snake venom GIIA sPLA, which shares structural and functional features with mammalian GIIA sPLAs, activates macrophage defense functions including lipid droplet (LDs) formation, organelle involved in both lipid metabolism and inflammatory processes. Macrophages (Ms) loaded with LDs, termed foam cells, characterize early blood vessel fatty-streak lesions during atherosclerosis. However, the factors involved in foam cell formation induced by a GIIA sPLA are still unknown.

Origin and characterization of small membranous vesicles present in the venom of Crotalus durissus terrificus.

Small membranous vesicles are small closed fragments of membrane. They are released from multivesicular bodies (exosomes) or shed from the surface membrane (microvesicles). They contains various bioactive molecules and their molecular composition varies depending on their cellular origin.

A snake venom group IIA PLA with immunomodulatory activity induces formation of lipid droplets containing 15-d-PGJ in macrophages.

Crotoxin B (CB) is a catalytically active group IIA sPLA from Crotalus durissus terrificus snake venom. In contrast to most GIIA sPLAs, CB exhibits anti-inflammatory effects, including the ability to inhibit leukocyte functions. Lipid droplets (LDs) are lipid-rich organelles associated with inflammation and recognized as a site for the synthesis of inflammatory lipid mediators.

Critical role of TLR2 and MyD88 for functional response of macrophages to a group IIA-secreted phospholipase A2 from snake venom.

The snake venom MT-III is a group IIA secreted phospholipase A2 (sPLA2) enzyme with functional and structural similarities with mammalian pro-inflammatory sPLA2s of the same group. Previously, we demonstrated that MT-III directly activates the innate inflammatory response of macrophages, including release of inflammatory mediators and formation of lipid droplets (LDs). However, the mechanisms coordinating these processes remain unclear.

Viperid venom glands with defective venom production. Morphological study.

The venom of viperid snakes is collected monthly at Butantan Institute for research purposes and production of antivenoms. Here we describe histological and ultrastructural changes on Crotalus durissus terrificus and Bothrops sp. venom glands with defective venom production.

A Lys49 phospholipase A2, isolated from Bothrops asper snake venom, induces lipid droplet formation in macrophages which depends on distinct signaling pathways and the C-terminal region.

MT-II, a Lys49PLA2 homologue devoid of catalytic activity from B. asper venom, stimulates inflammatory events in macrophages. We investigated the ability of MT-II to induce formation of lipid droplets (LDs), key elements of inflammatory responses, in isolated macrophages and participation of protein kinases and intracellular PLA2s in this effect.