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Mitochondria and Embryo Viability
Published in Carlos Simón, Carmen Rubio, Handbook of Genetic Diagnostic Technologies in Reproductive Medicine, 2022
Irene Corachan Garcia, Laura Iñiguez Quiles, Antonio Diez-Juan
Reactive oxygen species (ROS) are highly reactive molecules that include diverse chemical species such as the superoxide anion, the hydroxyl radical, and hydrogen peroxide (H2O2) (15). About 1–2% of the molecular oxygen consumed during physiological respiration is converted into superoxide radicals (13). Mitochondrial ROS are generated in the ETC through one-electron carriers (15,16). Their direct interaction with mitochondrial proteins, lipids, and DNA results in lipid peroxidation, protein oxidation, and mitochondrial DNA (mtDNA) mutations (13,16). Indeed, as the majority of ROS are products of mitochondrial respiration, mitochondria are the major targets for their damaging effects (13,15).
Modifications of Cellular Radiation Damage
Published in Kedar N. Prasad, Handbook of RADIOBIOLOGY, 2020
One of the most general and best-known modifying agents of radiation damage is molecular oxygen. Its ability to potentiate radiation response is called the oxygen effect, which is expressed in terms of the oxygen enhancement ratio (OER):
Ascorbate and the Hypoxic Response in Cancer
Published in Qi Chen, Margreet C.M. Vissers, Cancer and Vitamin C, 2020
Christina Wohlrab, Caroline Kuiper, Gabi U. Dachs
The dioxygenase enzymes have an absolute substrate requirement for oxygen and are therefore capable of oxygen sensing [60,61]. Inadequate supply with either of the two substrates, molecular oxygen and 2-oxoglutarate, or limited availability of the cofactors, iron and ascorbate, impairs activity of the enzymes. Hence, under hypoxia, hydroxylation of the HIF-α subunit cannot occur, and consequently, the interaction with the VHL complex and CBP/p300 is impaired, leading to stabilization and activation of HIF [59].
Long non-coding RNA MEG3 and its genetic variant rs941576 are associated with rheumatoid arthritis pathogenesis in Egyptian patients
Published in Archives of Physiology and Biochemistry, 2022
Alaa S. Wahba, Maha E. Ibrahim, Noha M. Mesbah, Samy M. Saleh, Dina M. Abo-elmatty, Eman T. Mehanna
Under normoxic conditions, hydroxylation of HIF-1α by prolyl hydroxylases (PHDs) and factor inhibiting HIF asparaginyl hydroxylase (FIH) allows its recognition by the E3 ubiquitin ligase von Hippel-Lindau protein (VHL), ubiquitination and proteasomal degradation (Ivan et al.2001). Hypoxia decreases PHDs activity since they require molecular oxygen as a cofactor allowing translocation of stabilised HIF-α to the nucleus, dimerisation with HIF-β and binding with co-activators such as p300. This complex initiates transcription of hypoxia-regulated genes which contain hypoxia response elements (HREs) in the promoter regions (Quiñonez-Flores et al.2016). Results from this study agree with this, there was a significant increase in serum HIF-1α level in RA patients compared to healthy individuals.
Magnetic fields and apoptosis: a possible mechanism
Published in Electromagnetic Biology and Medicine, 2022
The spin state plays a pivotal role in all the redox reactions that are at the core of our metabolic machinery. Redox reactions involve the transfer of electrons from one reactant to another. These kinds of reactions are so important that our life depends on them. The synthesis of many complex molecules often requires the oxidation of their precursors, via the use of molecular oxygen. The reason why oxygen is so important in biology is its atomic structure, characterized by the presence of two uncoupled electron spins despite its even atomic number. According to Pauli’s principle, a fundamental principle in quantum physics, oxygen can be considered as an “electron lover,” due to the need of additional electrons to match the coupled spins, in search for stability, thus finally acting as an oxidant. The utilization of molecular oxygen is vital in many biological pathways and the ability of aerobic organisms to harness the power of molecular oxygen as a terminal electron acceptor in their respiratory cycles has revolutionized the evolution of life (Falkowski and Godfrey 2008). The presence of two uncoupled electrons in the oxygen atomic structure makes oxygen a di-radical, since when an electron is uncoupled we are usually dealing with an uncoupled spin or free radical.
Effects of indirect actions and oxygen on relative biological effectiveness: estimate of DSB inductions and conversions induced by therapeutic proton beams
Published in International Journal of Radiation Biology, 2020
Wei-Ren Luo, Fang-Hsin Chen, Ren-Jing Huang, Yu-Pin Chen, Ya-Yun Hsiao
Other factors, such as free radical scavengers and the intracellular oxygen concentration, also affect the outcome of indirect actions on DSB induction following proton irradiation (Stewart et al. 2011; Hashimoto et al. 2018). The yields of DNA damage can be reduced by the capture of OH and H+ radicals when dimethylsulphoxide (DMSO) acts as a free radical scavenger (Jacob and de la Torre 2017). In contrast, under aerobic conditions, the free radical R reacts with oxygen to form RO2, resulting in DNA damage. DNA damage can be more efficiently repaired under hypoxic conditions; when molecular oxygen is present, the DNA damage can become ‘fixed’, rendering the damage irreparable. This is generally referred to as the “oxygen fixation hypothesis” (Hall and Giaccia 2012).