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Immunocytochemical Detection Systems
Published in Lars-Inge Larsson, Immunocytochemistry: Theory and Practice, 2020
Many methods for conjugating HRP to IgG or to Fab fragments have been devised. These include the use of glutaraldehyde or other bifunctional reagents in one- or two-step procedures (cf. References 5, 6, 30, 52, 199, and 227) or takes advantage of the glycoprotein nature of HRP, which makes it possible (by periodate oxidation) to generate HRP-aldehyde, which subsequently reacts with primary amino groups on IgG.86,239,246 Careful attention must be paid to the molecular sizes, antibody reactivities, and enzyme activities of these and other antibody enzyme conjugates (for a recent extensive review see Ishikawa et al.158). The smaller the conjugate, the better the penetration into tissue, and much attention has been paid to preparation of HRP-Fab conjugates.192,199 In order to further minimize the size of conjugates, Gerber et al.106 have coupled the heme-octapeptide of cytochrome c to antibodies.
The minerals
Published in Geoffrey P. Webb, Nutrition, 2019
There are a number of important copper-containing proteins in the body and these include: Some types of superoxide dismutase which is involved in free radical disposal (see Chapter 13). Enzymes involved in the synthesis of the catecholamine group of nerve transmitters from tyrosine (e.g. adrenalin, noradrenalin and dopamine). Enzymes involved in the synthesis of the pigment melanin responsible for, amongst other things, skin pigmentation. Cytochrome c oxidase involved in the electron transfer system in mitochondria. Ceruloplasmin which is involved in the transport and oxidation of iron that is necessary for haemoglobin synthesis.
Inhibition of Colon Carcinogenesis*
Published in Herman Autrup, Gary M. Williams, Experimental Colon Carcinogenesis, 2019
Inhibition of colon carcinogenesis by antioxidants is multifaceted. At the membrane level polyunsaturated phospholipid components of biological membranes are highly susceptible to peroxidation. The free radicals generated can disrupt the structural and functional integrity of the membranes, alter transport properties, and cause potential damage of critical DNA, RNA, and protein targets. As free radical scavengers, antioxidants can protect against the insults caused by carcinogens as well as maintain control over normal endogenous peroxidation reactions. A recent report provides evidence for a defective mitochondrial membrane in DMH-induced colon adenocarcinoma in rats.28 DMH enhanced the lipid peroxidation rate by tumor mitochondria eight- to tenfold above normal tissue counterparts. In addition, the mitochondria from cancer cells exhibited a fourfold reduction in NADH-cytochrome c reductase activity.
N-Acetylcysteine and Safranal prevented the brain damage induced by hyperthyroidism in adult male rats
Published in Nutritional Neuroscience, 2022
Asmaa S. Shahat, Wafaa A. Hassan, Wael M. El-Sayed
If the cells are severely damaged and the cellular architecture is lost, cells may go through apoptosis. Mitochondria contain several apoptogenic proteins in the inter-membrane space. Cytochrome c is a key mediator of apoptosis; its efflux into cytosol initiates the formation of apoptosome and activates the initiator Caspase-9 with subsequent activation of death-inducing Caspase-3. The increase in pro-apoptotic markers in the current study may be attributed to the imbalance between pro- and anti-oxidants induced by hyperthyroidism. Increase in the levels of oxidants led to oxidation of proteins and DNA and LPO, cell dysfunction and eventually cell death. Caspases stimulated by ROS may induce further free radicals release from mitochondria during the beginning of apoptosis propagating further damage. Activation of Caspase-3 induces Caspase-activated DNase (CAD) endonuclease that degrades DNA within the nucleus and initiates chromatin condensation leading to DNA fragmentation [45]. The fragmentation of DNA is now considered an important factor in the etiology of many neurodegenerative diseases. In the present study and also in other studies [44, 45], the induction of hyperthyroidism caused a significant brain DNA damage as an end result of increased apoptosis.
Strategies for targeting undruggable targets
Published in Expert Opinion on Drug Discovery, 2022
Gong Zhang, Juan Zhang, Yuting Gao, Yangfeng Li, Yizhou Li
Bcl-2 inhibitors block the binding of BH3-only proteins (i.e., Bim, Puma) to Bcl-2 proteins, allowing for BH3-only proteins to activate Bak/Bax-induced mitochondrial outer membrane permeabilization. This leads to the release of cytochrome c, thus inducing cancer cell apoptosis. The structure of Bcl-2 protein family consists of two hydrophobic α-helices wrapped by 5–7 amphiphilic α-helices, forming hydrophobic groove as the binding site for pro-apoptotic proteins like Bak and Bax. The PPI interface of Bcl-2 and Bak/Bax covers an area of approximately 750 ~ 1500 Å2, which is flat and groove-lacking. Furthermore, no existing small-molecule partner is served as a starting point for inhibitor development. [14] All these characteristics leave Bcl-2 as an undruggable target for a long time. However, ‘Alanine scanning’ technology gave better insights into the interface, where P2 and P4 hydrophobic pockets of Bcl-2 protein predominated among the hot spots.
Conjugated linoleic acid protects brain mitochondrial function in acrolein induced male rats
Published in Toxicology Mechanisms and Methods, 2021
Birsen Aydın, Cansu Güler Şahin, Vedat Şekeroğlu, Zülal Atlı Şekeroğlu
Mitochondrial dysfunction and ROS production play a role in the basis of many neurological and neurodegenerative diseases (Trushina and McMurray 2007; Migliore and Coppedè 2009; Kausar et al. 2018). It has been stated that neurodegenerative diseases are directly related to increases in oxidative stress, oxidized proteins and mitochondrial dysfunction (Naoi et al. 2005). Decreases in cytochrome c oxidase activity and ATP level and increases in free radicals have been found in Alzheimer's disease (Cardoso et al. 2004). A very strong relationship has also been found between Parkinson's disease and mitochondrial dysfunction (Morais and De Strooper 2010). We observed in our study AC induced oxidative stress and mitochondrial dysfunction in rat brain. AC decreased GSH, Mn-SOD and GPx levels, whereas it increased LP and PC formation. ICDH, α-CGDH, complex I and complex IV activities, and ATP levels were suppressed with the effect of AC. The results of the present study also clearly demonstrate that CLA exhibited protective activities against AC-induced toxicity in rat brain as evidenced by GSH, GPx, MnSOD, PC, LP, ICDH, α-CGDH, complex I, complex IV, and ATP levels. Therefore, CLA can play a beneficial role in reducing and improving oxidative stress and mitochondrial dysfunction in the brain in many neurological and neurodegenerative diseases.