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Mitochondrial Dysfunction in Huntington Disease
Published in Abhai Kumar, Debasis Bagchi, Antioxidants and Functional Foods for Neurodegenerative Disorders, 2021
Md. Hafiz Uddin, Marufa Rumman, Tasnuva Sarowar
The mPTP is a nonspecific channel whose activation is associated with mitochondrial defects and has been demonstrated to be involved in several HD models (Wong and Cuervo 2010; Gottlieb and Carreira 2010; Komatsu et al. 2006; Banerjee, Beal, and Thomas 2010; Yang et al. 2005; Webb et al. 2003; Tian et al. 2012). This is a structure on the mitochondrial membrane that mainly consists of three proteins—cyclophylin D (CypD) located in the mitochondrial matrix, voltage-dependent anion channel (VDAC) found in the outer mitochondria membrane, and adenine nucleotide translocator located in the mitochondrial inner membrane; and their dysregulated interaction participate in neurodegeneration (Liu et al. 2009; Chu et al. 2009; Yang et al. 2006). Mutant HTT increases sensitivity to calcium-induced mPTP opening of mitochondria resulting in apoptotic cell death of neurons (Jin and Johnson 2010). In vitro and in vivo studies have demonstrated that mitochondria isolated from striatal neurons of HD mice have reduced calcium uptake capacity and enhanced sensitivity to calcium-induced mitochondrial membrane depolarization, which is associated with increased sensitivity of the mPTP (Fernandes et al. 2007; Milakovic, Quintanilla, and Johnson 2006; Lim et al. 2008). The mPTP is highly sensitive to the changes in intracellular calcium levels as well as oxidative stress (Tian et al. 2012) and contributes to mitochondrial permeability, matrix swelling, and uncoupling of the oxidative phosphorylation that leads to deficits of respiration (Battisti et al. 2008).
Mechanisms of Antibiotic Resistance in Acinetobacter spp. — Genetics of Resistance
Published in E. Bergogne-Bénézin, M.L. Joly-Guillou, K.J. Towner, Acinetobacter, 2020
Aminoglycoside resistance in Gram-negative bacteria results most commonly from the action of plasmid- or transposon-encoded aminoglycoside-modifying enzymes which render aminoglycosides inactive. Three different types of modifying enzymes have been described: acetyltransferases (AAC), adenyl- or nucleotidyltransferases (AAD or ANT), and phosphotransferases (APH). Enzymes within each group are classified according to the aminoglycoside site of modifica-tion. Thus, there are four classes of acetyltransferases, AAC(l), AAC(3), AAC(6’) and AAC(2’), five of adenyltransferases, ANT(2"), ANT(3"), ANT(4’), ANT(6) and ANT(9), and five of phosphotransferases, APH(2"), APH(3’), APH(3"), APH(6) and APH(4). Several of the enzymes can be subdivided further according to their aminoglycoside resistance profile (designated by a Roman numeral suffix) and unique protein nature (designated by a lower-case alphabetical suffix). Hence, AAC(6’)-Ia and AAC(6’)-Ib express identical aminoglycoside resistance profiles, but differ in their protein sequence (Shaw et al., 1993).
Pseudomonas aeruginosa
Published in Firza Alexander Gronthoud, Practical Clinical Microbiology and Infectious Diseases, 2020
Aminoglycoside-modifying enzymes (AME) Acetyltransferases (AAC), phosphotransferases (APH) and nucleotidyltransferases (ANT).Among aminoglycoside resistance, resistance to gentamicin develops first followed by tobramycin and later on amikacin.Tobramycin is more potent against P. aeruginosa than gentamicin.
Lucialdehyde B suppresses proliferation and induces mitochondria-dependent apoptosis in nasopharyngeal carcinoma CNE2 cells
Published in Pharmaceutical Biology, 2023
Lingxue Liu, Zhangning Yu, Jing Chen, Benchen Liu, Changhui Wu, Ye Li, Jianhua Xu, Peng Li
ROS mainly originate from the mitochondria and the mitochondria are the main site of ROS-induced damage (Farías et al. 2017). The presence of a large number of ROS oxidizes the thiol group of adenine nucleotide translocase (ANT) and causes the excessive opening of mPTP, which leads to an increase in the permeability of the mitochondrial membrane and a decrease in MMP (Boyman et al. 2019). As a multifunctional second messenger, Ca2+ plays an essential role in the production of ROS (Sabharwal and Schumacker 2014). The excessive accumulation of mitochondrial Ca2+ may also trigger mPTP opening, thereby decreasing the MMP (Wang et al. 2019). As cell-death inducers, Ca2+ and ROS can activate the mitochondrial pathway (Dong et al. 2017). The results of the present study showed that LB significantly increased the ROS level and Ca2+ content in CNE2 cells, suggesting that LB activated the mitochondrial pathway to induce CNE2 cells apoptosis through the accumulation of ROS and calcium.
Protective effects and mechanism of action of ruscogenin in a mouse model of ovalbumin-induced asthma
Published in Journal of Asthma, 2022
Shanshan Zhan, Wei Wang, Lingfei Kong
Oxidative stress is generated when the free radical content exceeds the antioxidant capability. Free radicals are generally either reactive nitrogen radicals or ROS such as hydroxyl radicals, superoxide radical anions, and hydrogen peroxide (25). Mitochondria are the primary source of cellular ROS. The cross-linking of ROS with specific sulfhydryl groups results in stabilization of the cytoplasmic, or “c” conformation of the adenine nucleotide translocator, which interacts with VDAC to regulate downstream apoptotic signals (26). In MAM, VDAC1 directly interacts with molecules such as IP3R and GRP75, resulting in the release of calcium from the ER (27). When VDAC1 exists in an open state, the calcium ion levels are maintained by the mitochondrial calcium uniporter (MCU) and Na+/H+/Ca2+/NA+ reverse transporters. When compounds targeting VDAC1 alter the conformation of VDAC1 (resulting in a closed conformation), the calcium level in the intermembrane space increases, resulting in activation of the MCU and overloading of the mitochondria (28). An enhanced mitochondrial calcium level results in alteration of the mitochondrial membrane potential, thereby triggering the opening of the mitochondrial permeability transition pore, which in turn stimulates the release of cytochrome C into the cytoplasm, ultimately resulting in apoptosis (29).
Targeting glucose metabolism to develop anticancer treatments and therapeutic patents
Published in Expert Opinion on Therapeutic Patents, 2022
Yan Zhou, Yizhen Guo, Kin Yip Tam
As shown in Figure 1(b), cancer cells promote the first irreversible step of glycolysis by accelerating glucose uptake, as well as upregulating hexokinases (HKs) including HK1 and HK2. The facilitation of this critical step subtly prevents glucose from escaping from the cell through glucose transporters. Most notably, HK2, which binds to the outer membrane of mitochondria, plays a crucial role in cancer cells by cooperating with four pivotal partners including plasma membrane glucose transporter (Glut), the mitochondrial voltage-dependent anion channel (VDAC), the ATP synthase located in the inner mitochondrial membrane and the adenine nucleotide translocator that transports the ATP to the VDAC-HK2 complex [5]. In addition to these delicate collaborations that greatly facilitate glycolysis and subsequent biosynthesis, HK2 is essential to help cancer cells evade mitochondrial-induced apoptosis by binding to VDAC [6].