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Host Defense and Parasite Evasion
Published in Eric S. Loker, Bruce V. Hofkin, Parasitology, 2023
Eric S. Loker, Bruce V. Hofkin
Some intracellular parasites also interfere with apoptosis, ordinarily a key defense against such parasites. By preventing apoptosis, parasites extend the life of their host cell until their replication within the cell is complete. Eimeria tenella, to cite one example, invades epithelial cells in the intestinal ceca of chickens. This serious pathogen can cause high mortality, especially in young birds. Early in an infection, the parasite causes activation of a host cell transcription factor, resulting in the increased expression of proteins that block an apoptotic response. Likewise, T. gondii employs several mechanisms to ensure that infected cells do not undergo apoptosis. The cell death that is characteristic of apoptosis is often preceded by the release of cytochrome C from mitochondria. This cytochrome, in turn, initiates caspase activation. Once it is activated, caspase, in turn, activates caspase-activated DNAase (CAD), which degrades the cell’s DNA effectively killing it. But in T. gondii-infected cells, the parasite stimulates the up-regulation of Bcl-2 and Heat Shock Protein 70, two host proteins which reduce cytochrome C release, thereby preventing caspase activation and subsequent apoptosis.
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
Mitochondrial respiratory chain complexes consist of NADH-ubiquinone oxidoreductase (complex I), succinate ubiquinone oxidoreductase (complex II), ubiquinone-cytochrome c reductase (complex III), cytochrome c oxidase (complex IV), and ATP synthase (complex V). In addition, there are two electron carriers—ubiquinone (coenzyme Q) and cytochrome c—located in the inner mitochondrial membrane and intermembrane space respectively (Schon and Manfredi 2003). Altered ETS in HD pathology indicates the role of mitochondria in neurodegeneration (Sack 2010). In the development of HD, a decrease in the activity of the mitochondrial complexes I, II, III, and IV has been reported. The mutant huntingtin (mHTT) compromises complex II activity as well as ATP production and the Ca2+ buffering capacity (Parker et al. 1990; Gu et al. 1996; Browne et al. 1997).
Drug Design, Synthesis, and Development
Published in Nathan Keighley, Miraculous Medicines and the Chemistry of Drug Design, 2020
Metabolism by Cytochrome p450 enzymes is also affected by other chemicals. For example, other drugs and even certain foods can influence these processes. For certain drugs, brussel sprouts and cigarette smoke can enhance activity, whereas grapefruit juice suppresses it. Because a person’s diet can influence how a drug is metabolised, recommendations are usually given regarding what foodstuff should be eaten while taking the medication. For example, the immunosuppressant drug cyclosporine has improved activity if taken with grape fruit juice; being less speedily metabolised, but if the antihistamine terfenadine, which is a pro-drug, is taken with grapefruit juice, inhibition of metabolism that produces the active compound means that terfenadine persists in the body and can have cardiovascular side effects; hence, the active ingredient is now administered directly and is marketed as Allegra.
Cytochrome c injection induced embryo loss
Published in Drug and Chemical Toxicology, 2021
Tonghui Xu, Qiuhong Yang, Banqin Wang, Wenfu Wang, Jingxin Li, Yuyan Ma, Xiaolin Gao
Cytochrome c plays an important role in electron transfer between cytochrome c oxidase and reductase (Margalit and Schejter 1973). Normally, cytochrome c resides between the inner and outer mitochondrial membrane. At present, cytochrome c has been used as first-aid in the clinic for organs which are lacking oxygen. However, intriguingly based on more recent evidence, injection of cytochrome C has been shown to result in selective suicide of dendritic cells (DCs) (Lin et al.2008) and failure of self-tolerance (Qiu et al.2009). It is widely believed that decidual antigen-presenting cells (APCs), especially DCs, are critical for fetomaternal tolerance (Blois et al.2004, Blois et al.2007). In vivo DCs depletion affects implantation and early placental development in mice (Krey et al.2008). Cross talk between DCs and natural killer cells at the feto-maternal interface is also believed to be pivotal for pregnancy (Laskarin et al.2007). As a failure of self-tolerance result, recurrent spontaneous abortion (RSA) occurs in pregnant women. This type of abortion has been related to a shift in the T helper 2 (Th2) cell response of normal pregnancy to a Th1 response, where cytokines such as interferon-γ (INF-γ) and tumor necrosis factor-α (TNF‐α) can destroy trophoblasts (Raghupathy 1997). Therefore, we hypothesized that transient ablation of decidual DCs by cytochrome c injection may result in failed fetomaternal tolerance induction and Th1/Th2 imbalances, triggering embryo loss and abortion.
Co-delivery of quercetin and caffeic-acid phenethyl ester by polymeric nanoparticles for improved antitumor efficacy in colon cancer cells
Published in Journal of Microencapsulation, 2021
Reyhan Dilsu Colpan, Aysegul Erdemir
Bcl-2 protein family members and caspases are some of the key proteins involved in apoptosis process (Jan 2019). In order to evaluate how QuCaNP-3 induces apoptosis, changes in mRNA expression of Bax, Bcl-2, cytochrome-c, caspase-3, caspase-8 and caspase-9 genes were determined by qRT-PCR (Figure 6(a)). Both treatment with QuCaNP-3 and quercetin-CAPE resulted in an inverse relationship between Bcl-2 and Bax genes. Cytochrome-c expression was 3 times higher than control after quercetin-CAPE treatment. More importantly, QuCaNP-3 treatment increased cytochrome-c mRNA levels 5 fold than control. Cytochrome-c is an important protein involved in intrinsic apoptosis pathway. The increase in cytochrome-c mRNA levels after QuCaNP-3 treatment suggests activation of intrinsic apoptosis pathway through internalisation of nanoparticles by HT-29 cells.
Effect of CYP2C9 genetic polymorphism and breviscapine on losartan pharmacokinetics in healthy subjects
Published in Xenobiotica, 2021
Hang-Xing Huang, He Wu, Yingying Zhao, Tao Zhou, Xin Ai, Yu Dong, Yan Zhang, Yong Lai
Changes in drug-metabolizing enzyme activity were one of the links in clinical drug interactions. Hence, the interaction between breviscapine and other drugs was worthy of notice. Cytochrome P450 (CYP450) enzymes were important drug-metabolizing enzymes in the human body, which were involved in more than 70% of clinical drug metabolism and its polymorphisms can be used by clinicians to help determine therapeutic strategies, as well as therapeutic doses of drugs metabolised by CYP gene products (Pelkonen et al.2008, Manikandan and Nagini 2018). CYP2C9 was a subfamily with the CYP2C that accounting for 20% in the total content of human liver microsomal CYP450 enzymes. CYP2C9 enzymes participate in more than 10% of the clinical drug metabolism, which was deserved to be taken into account. Among the identified allelic variants of CYP2C9, the most important ones were CYP2C9*2 and CYP2C9*3. The CYP2C9*3 variant has been well studied in the literature where the activity of many drug substrates metabolised by this enzyme was reduced (Lee et al.2002, Kirchheiner and Brockmoller 2005, Pedreros-Rosales et al.2019). Genetic polymorphism of CYP2C9 plays an important role in CYP2C9 enzyme activity, and it was also one of the many facets important of reasons for the differences in the process of individual drug metabolism.