The Effects Of Alveolar Type II : The Causes Of Ati Cells

Succinate dehydrogenase is an enzyme found in the mitochondrial inner membrane. The enzyme catalyzes the reaction of oxidizing its substrate, succinate, into fumarate via the removal of hydrogen ions from succinate. This oxidation is vital in the Krebs cycle.

The first enzyme marker used was Succinate Dehydrogenase which catalyses the oxidation of succinate to fumarate in the tricarboxylic acid cycle (Hollywood, et al., 2010). This cycle occurs within mitochondria and succinate dehydrogenase is specifically found within the inner mitochondrial membrane. Therefore, succinate dehydrogenase activity is an indicator of mitochondrial activity (Berg, et al., 2007). Mitochondria are large organelles, approximately 0.5-1m in diameter and 5-10m in length with a high

With all living organisms, a process known as cell respiration is integral in order to provide the body with an essential form of energy, adenosine triphosphate (ATP). Oxygen, although an essential part of this process, can form reactants from colliding with electrons associated with carrier molecules. (pb101.rcsb.org, 2017). Hydrogen peroxide is an integral product of this reaction but is known to impose negative effects on the body if high levels are introduced. Explicitly, this reaction is caused “If oxygen runs into (one of these) carrier molecules, the electron may be accidentally transferred to it. This converts oxygen into dangerous compounds such as superoxide radicals and hydrogen peroxide, which can attack the delicate sulphur atoms and metal ions in proteins.” (pdbh101.rcb.org, 2017). Research has suggested that the hydrogen peroxide can be converted into hydroxyl radicals, known to mutate DNA, which can potentially cause bodily harm due to DNA’s role in the synthesis of proteins. These radicals can cause detrimental effects on the human body, and studies have suggested a link to ageing. Due to the harmful effects of these H2o2, it is important that the body finds a way to dispose of hydrogen peroxide before concentrations are too great.

Main compounds of the enzymatic antioxidant system are three, namely, SOD, CAT and tT which have an important role in detoxifying of H2O2 and superoxide anion in cells. Ample of hepatotoxic drugs induces the liver damage by lipid peroxidation indirectly or directly. The proxy radicals are main factors that mediate lipid peroxidation leading to liver injury and kidney damage(41). MDA as a main reactive aldehyde appears during polyunsaturated fatty acid peroxidation in the biological

owever Levine,R et al concluded that methionine residues are more important than cysteine residues as an antioxidant defence. Oxidants can react with methionine to produce methionine sulfoxide and when exposed on the surface can protect the cell from oxidisation. Methionine sulfoxide can be reduced back to methionine by methionine sulfoxide reductase which allows the antioxidant process to function catalytically.

Jones, A. E. & H., G., 1963. Oxidation of succinate and the control of the citric acid cycle in the mitochondria of guinea-pig liver, mammary gland and kidney. Biochemical Journal, 87(3), p. 639–648.

In this lab, I investigated aerobic respiration in the Krebs cycle through the means of a color indicator. The Krebs cycle is a vital metabolic pathway that occurs in the mitochondria and produces energy utilized by living cells. In order for the Krebs cycle to occur, glucose needs to combine with oxygen. Furthermore, in this lab, I used Malonate as an inhibitor; a competitive inhibitor binds to an enzyme’s active site inhibiting the substrate from binding which ceases the production.

Besides the appearance of episodic focal inflammatory lesions, there is a more generalized and progressive disease process that results in slow axonal , neuronal degeneration and subsequent accumulation of neurologic disabilities. The pathogenesis of this neurodegenerative process is aurged to the mitochondrial dysfunction which could be a key contributing mechanism ( Su et al., 2013)

We further wanted to determine the level of DNA damage in ATII cells isolated from emphysema patients compared to control non-smokers or smokers. We analyzed phosphorylation of H2AX (γH2AX), which is a sensitive indicator of DSBs (REF), by Western blotting and immunohistofluorescence. We found significantly higher γH2AX phosphorylation in ATII cells obtained from smokers in comparison with non-smokers (p<0.05; Figs. 2a, b). Interestingly, ATII cells isolated from emphysema patients have lower expression of γH2AX phosphorylation in comparison with smokers. We also determined γH2AX phosphorylation in lung tissue sections by immunohistofluorescence using SP-A as a marker of ATII cells. We obtained similar results showing higher γH2AX florescence intensity in ATII cells obtained from smokers in comparison with control non-smokers and emphysema (p< 0.05; Figs. 2c, d). Although, ATII cells isolated from emphysema patients have higher ROS levels (Figs. 1a, b), they don’t show a significant increase in γH2AX phosphorylation. This may suggest the impairment of DSBs repair signaling leading to lack of the DNA damage repair in these cells.

Oxidants will affect mitochondrial redox status and may cause extensive oxidative damage to proteins(Kalyanaraman et al .,2002). Furthermore, the mitochondrial transition pore can open releasing cytochrome c and possibly affecting mitochondrial function. Cytochrome c can activate cytosolic caspases to induce apoptosis. Doxorubicin may induce anti-apoptotic (Bcl-2, Bcl-XL) and pro-apoptotic (Bax, Bad) proteins. The Bcl-2 family of proteins regulates the release of cytochrome c . These include Bax, Bad, and Bid, which are pro-apoptotic proteins that favor cytochrome c release and Bcl-2 and Bcl-XL which are anti-apoptotic proteins that inhibit cytochrome c release . The mechanisms of how Bcl-2 family proteins regulate release of cytochrome c and apoptogenic factors are under investigation.

To investigate the effects of SS-31 on the mitochondria in cells derived from FRDA patients, we detected MMP with the lipophilic dye JC-1 by measuring a potential-dependent shift in fluorescence from green to red, which reflected its aggregation in mitochondria29. The increased ratio of red versus green fluorescence in patient-derived cells after SS-31 treatment indicated more polarised mitochondria (Fig. 2a). Intracellular ATP level is another pivotal measure of mitochondrial quality. We found that SS-31 treatment significantly raised ATP levels in patient-derived cells (Fig. 2b), indicating increased oxidative phosphorylation. The ratio of NADH/NAD+ in patient-derived lymphoblasts was also measured and was found to be significantly reduced to the levels comparable to the healthy control cells (Fig. 2c). These results indicate much improvement of mitochondrial quality in patient-derived lymphoblasts post SS-31 treatment. Furthermore, we quantified the copy number of mitochondrial DNA and found that SS-31 treatment mildly increased the copy number of mitochondria in patient-derived lymphoblasts (Fig. 2d). Electron microscopic data substantiated these results revealing structural improvements from abnormal cristae in patient-derived cells to regular invagination of the inner membrane after SS-31 treatment (Fig. 2e). Taken together, SS-31 improved the

DATS basically mediates in thiol/Disulfide exchange by redox modification of specific reactive cysteines resulting in thiolyation of the protein like actin microfilament and β-tubulin causing depolymerization of actin filament and microtubule leading to M-Phase cell cycle arrest.(26)

Mitochondria play a key role in the apoptotic process, being involved in two distinct signaling pathways: (1) maintenance of ATP production, and (2) mitochondrial membrane potential and mitochondrial membrane permeability. The mitochondrial membrane potential results from the difference in the electrical potential generated by the electrochemical gradient across the inner membrane, which is critical for maintaining the physiological function of the respiratory chain to generate ATP. Therefore, changes in the ∆Ψm have been originally proposed to be early and obligate events in the apoptotic signaling pathway.

The implication that protein degradation pathways are dysregulated by hyperoxia is especially important given that not only is it implicated in aging within the lung, but that the mitochondrial dysregulation not only seen at work within this body of literature, but also the right ventricles used in this study would suggest that protein degradation could play a role in the right ventricular dysfunction found after exposure to post-natal hyperoxia (Goss, 2017).

Based on this view, diminished secretion of Prx1 could be a benefit for F2HIC-matured DCs. In contrast to this view, some recent studies have shown that low expression of Prx1 sensitizes different cells to reactive oxygen species during oxidative stress and Prx1 protects cells against oxidative stress by reducing apoptosis (Gordeeva et al. , 2015, He et al. , 2014, Yuan et al. , 2004). Based on this data, we can suggest that F2HIC-matured DCs may be more sensitive during oxidative stress.