China
Africa
Explore chapters and articles related to this topic
Role of Mitochondrial Injury During Oxidative Injury to Hepatocytes: Evidence of a Mitochondrial Permeability Transition by Laser Scanning Confocal Microscopy
Published in John J. Lemasters, Constance Oliver, Cell Biology of Trauma, 2020
Anna-Liisa Nieminen, Roberto Imberti, Alice K. Saylor, Samuel A. Tesfai, Brian Herman, John J. Lemasters
Cyanide-induced cell killing is markedly reduced by intracellular acidification.2,9 Intracellular acidosis due to metabolic acid accumulation during glycolytic metabolism of fructose might thus explain protection by fructose. In such a scenario, CCCP, a protonophore, should block fructose-induced intracellular acidification and thereby accelerate cell killing. However, this hypothesis cannot explain how oligomycin reverses the CCCP effect. To examine further the importance of changes of intracellular pH on fructose protection, we treated hepatocytes with the Na+/H+ ionophore, monensin, at low extracellular Na+ concentration, which clamped intracellular pH to extracellular pH.9 Under these pH-clamped conditions, fructose retained is protective effect.3 Thus, we cannot explain fructose protection by changes of intracellular pH.
Gastrointestinal Tract
Published in Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard, Toxicologic Pathology, 2018
Judit E. Markovits, Graham R. Betton, Donald N. McMartin, Theresa Boulineau
Parietal cell vacuolation is seen after high-dose administration of antisecretory compounds. Omeprazole is acid-activated to covalently bind to H+/K+ ATPase proton pump to suppress gastric acid output to treat peptic ulcer disease and gastro-esophageal reflux disease (GERD). At high toxicological doses, proton pump inhibitors (PPIs) can cause selective parietal cell vacuolation and single cell necrosis. The parietal cell protonophore DMP-777 depletes parietal cells (Nomura et al. 2005; Nozaki et al. 2008).
Natural Products as an Effective Treatment Option for Depression
Published in Vikas Kumar, Addepalli Veeranjaneyulu, Herbs for Diabetes and Neurological Disease Management, 2018
Yogesh Anant Kulkarni, Kalyani Himanshu Barve, Ginpreet Kaur
Hyperforin, a prenylated phloroglucinol, isolated from the flowers of this plant is the most active form and has been reported to treat mild to moderate depression. The mechanisms of hyperforin actions are not yet understood, but may include inhibition of 5-lipoxygenase, high affinity binding to the pregnane X receptor, release of Ca2+ and/or Zn2+ from intracellular stores, and affecting of presynaptic and vesicular uptake, storage and release of neurotransmitters such as serotonin, dopamine, norepinephrine, acetylcholine, GABA, and glutamate. It is also believed that the activity is due to TRPC6 channel activation and hyperforin acts as a protonophore which causes cytosolic acidification, in turn activating the plasma membrane sodium-proton exchanger. Thereby the free intracellular sodium concentration increases and the neurotransmitter uptake by Na+ cotransport is inhibited. Additionally, hyperforin depletes and reduces loading of large dense core vesicles in chromaffin cells, which requires a pH gradient in order to accumulate monoamines.41
GPIb-IX-V and platelet clearance
Published in Platelets, 2022
The platelet apoptotic machinery is primarily a regulator of platelet lifespan, rather than activity. Briefly, platelet apoptosis depends on Bcl2-family proteins, specifically Bcl-xL [44,45], to restrain the pro-apoptotic molecules Bax and Bak, which mediate mitochondrial damage [46]. Some of the same signaling events that facilitate platelet apoptosis are also downstream of GPIb-IX-V activation, including calcium flux [14,47] and phosphatidylserine (PS) exposure [11,48]. One study has shown elevation of pro-death molecules Bax/Bak and mitochondrial depolarization downstream of the GPIbα-VWF interaction, dependent on 14-3-3ζ association with the cytoplasmic tail of GPIbα[49]. In the intrinsic pathway of apoptosis, mitochondrial outer membrane permeabilization (MOMP) is a critical step resulting in loss of the mitochondrial electrochemical gradient. When MOMP is induced in platelets prior to transfusion via treatment with carbonyl cyanide 3-chlorophenylhydrazone (CCCP), a lipid-soluble protonophore, they are cleared rapidly in vivo [42]. CCCP treatment also leads to significant ectodomain shedding of GPIbα. However, while mitochondrial damage is linked to GPIb-IX-V shedding, and the GPIbα-VWF interaction is linked to mitochondrial depolarization, a mechanistic understanding of these relationships remains elusive, and remains to be seen whether any other components of the intrinsic apoptosis pathway are engaged by GPIb-IX-V.
Synthesis and biological evaluation of alpha-bromoacryloylamido indolyl pyridinyl propenones as potent apoptotic inducers in human leukaemia cells
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2018
Romeo Romagnoli, Filippo Prencipe, Luisa Carlota Lopez-Cara, Paola Oliva, Stefania Baraldi, Pier Giovanni Baraldi, Francisco Estévez-Sarmiento, José Quintana, Francisco Estévez
Increasing evidence indicated that mitochondria play a vital role in the progression of apoptosis62. The dissipation of the electrochemical gradient (ΔΨm) created by the proteins of the respiratory chain located on the inner mitochondrial membrane is also a key event in mitochondria-controlled apoptotic pathways63. To examine whether a disruption of the mitochondrial membrane potential (ΔΨm) is involved in the mechanism of cell death, U-937 cells were treated with increasing concentrations of 4a, stained using the dye 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolcarbocyanine (JC-1) to monitor changes in ΔΨm induced by 4a and analysed by flow cytometry. Figure 6(F) indicates that ΔΨm dropped after 4 h of treatment at different concentrations (0.1, 0.3, and 1 μM), which suggests that the dissipation of the mitochondrial membrane potential contributed to apoptosis induced by the hybrid compound 4a. After a 4 h treatment of U-937 cells at two different concentrations (0.3 and 1 μM) of 4a, the results showed in Figure 6(G) indicated a shift toward the JC-1 monomers, with the fluorescence which increased from 1.4% to 23.6%, which was consistent with a corresponding decrease of the JC-1 aggregates. In this study, the protonophore carbonyl cyanide m-chlorophenyl hydrazone (CCCP, 50 μM) that depolarizes mitochondrial membranes, was used as a positive control.
An antimicrobial metabolite n- hexadecenoic acid from marine sponge-associated bacteria Bacillus subtilis effectively inhibited biofilm forming multidrug-resistant P. aeruginosa
Published in Biofouling, 2023
Arya Sajayan, Amrudha Ravindran, Joseph Selvin, Prathiviraj Ragothaman, George Seghal Kiran
Based on IR spectroscopy and GC-MS analysis, the active antimicrobial compound was structurally identified as n-hexadecanoic acid (palmitic acid; C16:0). N-hexadecanoic acid or palmitic acid is one of the fatty acids most commonly found in microbes, plants, and animals and exhibits antibacterial properties against pathogens. Palmitic acid is reported to inhibit virulence factors of many pathogens, including P. aeruginosa, Candida tropicalis, and Neisseria gonorrhoeae (Miller et al. 1977; Inoue et al. 2008; Prasath et al. 2020). The presence of palmitic acid in B. subtilis has already been reported, and the acid helps bacteria to contribute to environmental adaptation by improving resistance against the protonophore (Diomandé et al. 2015).