Muscle proteolysis via ubiquitin-proteasome system (UPS) is activated by BthTx-I Lys49 PLA2 but not by BthTx-II Asp49 PLA2 and Bothrops jararacussu venom

Exploring the ability of low-level laser irradiation to reduce myonecrosis and increase Myogenin transcription after Bothrops jararacussu envenomation

“…Recent study of ours showed late MyoD protein expression in mice gastrocnemius exposed to same dose of Bjssu [11]. In relation to saline sham animals, we found that the MyoD protein translation in envenomed muscle increased later at 96 h, while MyoG increased before, at 72 h, thus correlating herein with MyoG increase and unaltered MyoD until the 72 h after envenomation.…”

“…sub-lethal dose of 830 µg/kg of Bjssu (volume of 20 µL), which was injected into the medial portion of the right gastrocnemius muscle after skin shaving and gentle animal contention. Bjssu sublethal dose (830 µg/kg) was previously established by Vieira et al [36,38] and Kenzo-Kagawa et al [11]. Control mice (S48, SL48, SPL48, S72, SL72, and SPL72 groups) were injected with 0.9% saline solution (NaCl, volume of 20 µL, same route as for Bjssu).…”

“…The PLA 2 s present in the venom disrupt the cell membrane and compromise the mechanisms of energy production, the mitochondrial intermembrane ion exchange, and cellular respiration, leading to tissue necrosis [9,10]. Recently, we have shown that the crude Bjssu and its BThTx-I and BthTx-II PLA 2 myotoxins differentially inhibit the pro-myogenic regulatory factors (MRFs) expression, and activate the negative regulators of myogenesis, such as myostatin and members of ubiquitin proteasome system [11].…”

Benefits of Sebastiania hispida (Euphorbiaceae) extract and photobiomodulation therapy as potentially adjunctive strategies to be explored against snake envenoming

“…In contrast, myonecrotic myofibers were evident in VBm places reached by the venom. This myolytic action is mainly promoted by myotoxins, such as PLA 2 and PLA 2 homologues [51,62], which disrupts sarcolemma and leads to fibers proteolysis through ubiquitin-proteasome system (UPS) activation, as demonstrated by Kenzo-Kagawa et al [17], in a model of B. jararacussu venom-induced myonecrosis in mice gastrocnemius.…”

“…Serum therapy is traditionally used for neutralizing systemic alterations but display no effectiveness against local damage caused by snakebite [14]. Phospholipases A 2 (PLA 2 ) myotoxins, such as Lys49 PLA 2 homologue and Asp49 PLA 2 and blood disturbance enzymes contained in venom rapidly disseminate and cause fast destruction of soft tissues before victims can reach clinical support [15][16][17]. A syndromic set of molecular and cellular alterations starting with PLA 2 -induced rupture of cell membrane are activated producing pain, thrombolysis, blood incoagulability, local anoxia, oxidative stress, edema, and myonecrosis, whose severity may result in permanent sequelae and even amputation of the envenomed member [18].…”