Effects of Lonomia obliqua Venom on Vascular Smooth Muscle Cells: Contribution of NADPH Oxidase-Derived Reactive Oxygen Species

• Published in: Toxins Vol. 9; no. 11; p. 360
• Main Authors: Moraes, João Alfredo, Rodrigues, Genilson, Nascimento-Silva, Vany, Renovato-Martins, Mariana, Berger, Markus, Guimarães, Jorge Almeida, Barja-Fidalgo, Christina
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 07-11-2017; MDPI
• Subjects: Actin; Activation; Animals; Arthropod Venoms - toxicity; Blood coagulation; Blood vessels; Cell Line; Cell Movement - drug effects; Cell proliferation; Cell Proliferation - drug effects; Cell Survival - drug effects; Cytoskeleton; Endothelial cells; Extracellular signal-regulated kinase; Flavonoids - pharmacology; Focal adhesion kinase; Inflammation; Larva; Lepidoptera; Lonomia obliqua venom; Mitochondria; Mitogen-Activated Protein Kinase 1 - antagonists & inhibitors; Mitogen-Activated Protein Kinase 1 - metabolism; Muscle, Smooth, Vascular - cytology; Muscles; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - metabolism; Myocytes, Smooth Muscle - physiology; NAD(P)H oxidase; NADPH Oxidases - metabolism; Oxidase; Phosphorylation; Protein Kinase Inhibitors - pharmacology; Rats; Reactive oxygen species; Reactive Oxygen Species - metabolism; Smooth muscle; vascular smooth muscle cells; Venom; vascular smooth muscle cells; reactive oxygen species; Lonomia obliqua venom
• ISSN: 2072-6651; 2072-6651
• DOI: 10.3390/toxins9110360

Envenomation caused by human contact with the caterpillar Lonomia is characterized by deleterious effects on coagulation and patency of blood vessels. The cellular effects induced by
venom highlights its capacity to activate endothelial cells, leading to a proinflammatory phenotype. Having more knowledge about the mechanisms involved in envenomation may contribute to better treatment. We aimed to evaluate the effects of
caterpillar bristle extract (LOCBE) on vascular smooth muscle cells (VSMC). We observed that LOCBE induced VSMC migration, which was preceded by alterations in actin cytoskeleton dynamics and Focal Adhesion Kinase activation. LOCBE also induced Extracellular Signal-Regulated Kinase (ERK) phosphorylation in VSMC, and the inhibition of this pathway impaired cell proliferation. Stimulation of VSMC with LOCBE triggered reactive oxygen species (ROS) production through the activation of NADPH oxidase. The rapid increase in these ROS further induced mitochondrial ROS production, however only NADPH oxidase-derived ROS were involved in ERK activation in VSMC. We that demonstrated the chemotactic and proliferative effects of LOCBE on VSMC were dependent on ROS production, mainly through NADPH oxidase. Together, the data show that
venom can interact with and activate VSMC. These effects rely on ROS production, suggesting new potential targets for treatment against vascular damage during envenomation.