scholarly journals Cytotoxic mechanism of Bothrops jararaca venom mediated by mitochondrial depolarization

2020 ◽  
Vol 4 (1) ◽  
pp. 001-008
Author(s):  
Moras Ana Moira ◽  
Steffens Luiza ◽  
Nordio Bruna Eliza ◽  
Saffi Jenifer ◽  
Dallegrave Eliane ◽  
...  
Keyword(s):  
Mitochondrial Depolarization ◽  
Bothrops Jararaca ◽  
Cytotoxic Mechanism

Properties of Fibrinogen Cleaved by Jararhagin, a Metalloproteinase from the Venom of Bothrops jararaca

1994 ◽  
Vol 72 (02) ◽  
pp. 244-249 ◽  
Author(s):  
Aura S Kamiguti ◽  
Joseph R Slupsky ◽  
Mirko Zuzel ◽  
Charles R M Hay
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Fibrin Clot ◽  
Clot Formation ◽  
Human Fibrinogen ◽  
Activated Platelets ◽  
Bothrops Jararaca ◽  
Platelet Binding ◽  
Fibrin Monomers ◽  
Fibrinogen Molecule

SummaryHaemorrhagic metalloproteinases from Bothrops jararaca and other venoms degrade vessel-wall and plasma proteins involved in platelet plug and fibrin clot formation. These enzymes also cause proteolytic digestion of fibrinogen which has been suggested to cause defective platelet function. Fibrinogen degradation by jararhagin, a metalloproteinase from B. jararaca, and the effect of jararhagin fibrinogenolysis on both platelet aggregation and fibrin clot formation were investigated. Jararhagin was found to cleave human fibrinogen in the C-terminal region of the Aα-chain giving rise to a 285-290 kDa fibrinogen molecule lacking the Aα-chain RGD 572-574 platelet-binding site. Platelet binding and aggregation of ADP-activated platelets is unaffected by this modification. This indicates that the lost site is not essential for platelet aggregation, and that the remaining platelet binding sites located in the N-terminal portion of Aα chains (RGD 95-97) and the C-terminal of γ chains (dodecapeptide 400-411) are unaffected by jararhagin-digestion of fibrinogen. Fibrin clot formation with thrombin of this remnant fibrinogen molecule was defective, with poor polymerization of fibrin monomers but normal release of FPA. The abnormal polymerization could be explained by the loss of one of the two complementary polymerization sites required for side-by-side association of fibrin protofibrils. Jararhagin-induced inhibition of platelet function, an important cause of haemorrhage in envenomed patients, is not caused by proteolysis of fibrinogen, as had been thought, and the mechanism remains to be elucidated.

Singlet oxygen mediated DNA damage induced phototoxicity by ketoprofen resulting in mitochondrial depolarization and lysosomal destabilization

Toxicology ◽  
2013 ◽  
Vol 314 (2-3) ◽  
pp. 229-237 ◽  
Author(s):  
Ratan Singh Ray ◽  
Syed Faiz Mujtaba ◽  
Ashish Dwivedi ◽  
Neera Yadav ◽  
Ankit Verma ◽  
...  
Keyword(s):  
Dna Damage ◽  
Singlet Oxygen ◽  
Mitochondrial Depolarization

scholarly journals Activation of the oxygen-sensing signal cascade prevents mitochondrial injury after mouse liver ischemia-reperfusion

2008 ◽  
Vol 295 (4) ◽  
pp. G823-G832 ◽  
Author(s):  
Zhi Zhong ◽  
Venkat K. Ramshesh ◽  
Hasibur Rehman ◽  
Robert T. Currin ◽  
Vijayalakshmi Sridharan ◽  
...  
Keyword(s):  
Mitochondrial Permeability Transition ◽  
Oxygen Sensing ◽  
Ischemia Reperfusion ◽  
Multiphoton Microscopy ◽  
Specific Inhibitor ◽  
Permeability Transition ◽  
Heme Oxygenase 1 ◽  
Mitochondrial Depolarization ◽  
Signal Cascade

The mitochondrial permeability transition (MPT) plays an important role in hepatocyte death caused by ischemia-reperfusion (IR). This study investigated whether activation of the cellular oxygen-sensing signal cascade by prolyl hydroxylase inhibitors (PHI) protects against the MPT after hepatic IR. Ethyl 3,4-dihyroxybenzoate (EDHB, 100 mg/kg ip), a PHI, increased mouse hepatic hypoxia-inducible factor-1α and heme oxygenase-1 (HO-1). EDHB-treated and untreated mice were subjected to 1 h of warm ischemia to ∼70% of the liver followed by reperfusion. Mitochondrial polarization, cell death, and the MPT were assessed by intravital confocal/multiphoton microscopy of rhodamine 123, propidium iodide, and calcein. EDHB largely blunted alanine aminotransferase (ALT) release and necrosis after reperfusion. In vehicle-treated mice at 2 h after reperfusion, viable cells with depolarized mitochondria were 72%, and dead cells were 2%, indicating that depolarization preceded necrosis. Mitochondrial voids excluding calcein disappeared, indicating MPT onset in vivo. NIM811, a specific inhibitor of the MPT, blocked mitochondrial depolarization after IR, further confirming that mitochondrial depolarization was due to MPT onset. EDHB decreased mitochondrial depolarization to 16% and prevented the MPT. Tin protoporphyrin (10 μmol/kg sc), an HO-1 inhibitor, partially abrogated protection by EDHB against ALT release, necrosis, and mitochondrial depolarization. In conclusion, IR causes the MPT and mitochondrial dysfunction, leading to hepatocellular death. PHI prevents MPT onset and liver damage through an effect mediated partially by HO-1.

Essential roles of mitochondrial depolarization in neuron loss through microglial activation and attraction toward neurons

2013 ◽  
Vol 1505 ◽  
pp. 75-85 ◽  
Author(s):  
Min-Kyung Nam ◽  
Hyun-Ah Shin ◽  
Ji-Hye Han ◽  
Dae-Wook Park ◽  
Hyangshuk Rhim
Keyword(s):  
Microglial Activation ◽  
Mitochondrial Depolarization ◽  
Neuron Loss
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