Mitochondrial stress

There is also evidence that the stress-70 proteins interact with extended, or unfolded, polypeptides. It has been demonstrated that a mitochondrial stress-70 protein is essential for import of proteins into mitochondria (Kang et al., 1990 Ostermann 1990). More specifically, polypeptides bind to, and can be cross-linked to, the mitochondrial stress-70 protein during import (Scherer et ai, 1990). It has further been demonstrated that cytoplasmic stress-70 proteins are essential for efficient transmembrane translocation of proteins into mitochondria or mi-crosomes (Chirico et al, 1988 Deshaies et al, 1988) this has led to the suggestion that the cytoplasmic stress-70 proteins may bind to and stabilize extended, unfolded conformations of polypeptide prior to their transmembrane translocation. 

Mizzen, L. A., Kabiling, A. N., and Welch, W. J. (1991). The two mammalian mitochondrial stress proteins, grp 75 and hsp 58, transiently interact with newly synthesized mitochondrial proteins. Cell Regal. 2, 165—179. 

Scherer, P. E., Krieg, U. C., Hwang, S. T., Vestweber, D., and Schatz, G. (1990). A precursor protein partly translocated into yeast mitochondria is bound to a 70 kd mitochondrial stress protein. EMBO J. 9, 4315-4322. 

Additionally, apoptosis probably also plays a role in the AA-induced proximal tubular atrophy according to several in vivo and in vitro studies [66,68,70]. In an in vitro study conducted by Hsin et al [71], LLC-PKl cells exposed to AA showed a rapid increase in their intracellular calcium content leading to endoplasmic reticulum and mitochondrial stress which in turn causes activation of the caspase pathway and finally apoptosis. 

Shih AY, Imbeault S, Barakauskas V, Erb H, Jiang L, Li P, Murphy TH (2005) Induction of the Nrf2-driven antioxidant response corrfers neuroprotection dirring mitochondrial stress in vivo Shinkai Y, Sumi D, Fukami I, Ishii T, Kumagai Y (2006) Sulforaphane, an activator of Nrf2, suppresses cellular accumulation of arsoiic and its cytotoxicity in primary mouse hepatocytes. FEBS Lett 580 1771-1774... 

Cha, J.-D. and Kim, J. Y. (2012). Essential oil from Cryptomeria japonica induces apoptosis in human oral epidermoid carcinoma cells via mitochondrial stress and activation of caspases. Molecule 17,... 

Cha, J.-D., Moon, S.E., Kim, H.-Y., Cha, I.-H., and Lee, K.-Y. (2009a). Essential oil of Artemisia capillaris induces apoptosis in KB cells via mitochondrial stress and caspase activation mediated by MAPK-stimulated signaling pathway. oodSci. 75 9), T75-T81. 

Perhaps the most extensively studied activity of ginkgo is its antioxidant activity and it is probably the key to its significant protective effects. Numerous reports have appeared in recent literature that link such activity to neuroprotection, hepatoprotection, radioprotection,cancer chemoprevention and apoptosis,Alzheimer s disease (amyloid-beta protein inhibition), reduced cerebral ischemia/stroke, gastropro-tection (antiulcer), nephroprotection, reduced mitochondrial stress," "" and even skin disorders (vitiligo)." ... 

Deshaies, R.J., Koch, B.D., Wemer-Washbume, M., Craig, E.A., Schekman, R. (1988). kA subfamily of stress proteins facilitates translocation of secretory and mitochondrial precursor polypeptides. Nature 332,800-805. 

These include the mitochondrial respiratory chain, key enzymes in fatty acid and amino acid oxidation, and the citric acid cycle. Reoxidation of the reduced flavin in oxygenases and mixed-function oxidases proceeds by way of formation of the flavin radical and flavin hydroperoxide, with the intermediate generation of superoxide and perhydroxyl radicals and hydrogen peroxide. Because of this, flavin oxidases make a significant contribution to the total oxidant stress of the body. 

Augustin, W. et al.. Beta-carotene cleavage products induce oxidative stress by impairing mitochondrial functions brain mitochondria are more sensitive than liver mitochondria, Free Rad. Biol. Med., 33, S326, 2002. 

Recent studies by Crompton et al. have shown that oxidant stress may open a Ca-sensitive, non-selective pore in the inner mitochondrial membrane that is blocked by cyclosporin A (Crompton, 1990 Crompton and Costi, 1990). This pore opening results in massive mitochondrial swelling, dissipation of the transmembrane proton gradient and disruption of mitochondrial energy production (Crompton et al., 1992). Since mitochondria may play a role as a slow, high-capacity cytosolic calcium buffer (Isenberg et al., 1993), disruption of mitochondrial function may also contribute to calcium overload and cell injury. 

Deprived of their substrate in severe or prolonged hypoxia, some ATPase-driven systems, including ion pumps, may become impaired. Further, with the decrease in the availability of O2 as its terminal electron acceptor, the mitochondrial transport chain becomes increasingly unable to accept reducing equivalents from cellular metabolic processes. Hence the intracellular pH falls, subjecting the cell as a whole to a reductive stress and favouring those enzyme systems with acid pH optima. 

PD affects approximately one million Americans (1% of people over 60 years of age). The average age of onset is 60 years of age, and PD is fairly uncommon in those under age 40. The etiology of PD is unknown, but genetic predisposition, environmental factors, or combinations of these have been proposed to explain why nerve cells in the substantia nigra deteriorate. About 15% of patients with PD have a first-degree relative with the disease. The pathogenesis of cell death (neuron degeneration) may be due to oxidative stress, mitochondrial... 

It has been shown in many studies that protective effects of carotenoids can be observed only at small carotenoid concentrations, whereas at high concentrations carotenoids exert pro-oxidant effects via propagation of free radical damage (Chucair et al., 2007 Lowe et al., 1999 Palozza, 1998, 2001 Young and Lowe, 2001). For example, supplementation of rat retinal photoreceptors with small concentrations of lutein and zeaxanthin reduces apoptosis in photoreceptors, preserves mitochondrial potential, and prevents cytochrome c release from mitochondria subjected to oxidative stress induced by paraquat or hydrogen peroxide (Chucair et al., 2007). However, this protective effect has been observed only at low concentrations of xanthophylls, of 0.14 and 0.17 pM for lutein and zeaxanthin, respectively. Higher concentrations of carotenoids have led to deleterious effects (Chucair et al., 2007). 

It should be stressed that in the RPE transport of iron ions between the photoreceptors and choroidal blood supply is constantly occurring (He et al., 2007 Wong et al., 2007). Iron is essential for the proper function and survival of every cell as it serves as a co-factor for vital mitochondrial enzymes. 

Numerous studies have demonstrated that degradation products of (3-carotene exhibit deleterious effects in cellular systems (Alija et al., 2004, 2006 Hurst et al., 2005 Salerno et al., 2005 Siems et al., 2003). A mixture of (3-carotene degradation products exerts pro-apoptotic effects and cytotoxicity to human neutrophils (Salerno et al., 2005 Siems et al., 2003), and enhances the geno-toxic effects of oxidative stress in primary rat hepatocytes (Alija et al., 2004, 2006), as well as dramatically reduces mitochondrial activity in a human leukaemic cell line, K562, and RPE 28 SV4 cell line derived from stably transformed fetal human retinal pigmented epithelial cells (Hurst et al., 2005). As a result of degradation or enzymatic cleavage of (3-carotene, retinoids are formed, which are powerful modulators of cell proliferation, differentiation, and apoptosis (Blomhoff and Blomhoff, 2006). 

Siems, W, Sommerburg, O, Schild, L, Augustin, W, Langhans, CD, and Wiswedel, I, 2002. Beta-carotene cleavage products induce oxidative stress in vitro by impairing mitochondrial respiration. Faseb J 16,... 

In biochemical systems, acid-base and redox reactions are essential. Electron transfer plays an obvious, crucial role in photosynthesis, and redox reactions are central to the response to oxidative stress, and to the innate immune system and inflammatory response. Acid-base and proton transfer reactions are a part of most enzyme mechanisms, and are also closely linked to protein folding and stability. Proton and electron transfer are often coupled, as in almost all the steps of the mitochondrial respiratory chain. 

Similarly, abnormalities in the mitochondrial machinery and resulting oxidative stress may also intervene in Parkinson s disease (PD) [31, 32]. The decreased activity of mitochondrial complex I in PD patients [33], and the preferential toxicity of the complex I inhibitor rotenone [34] and MPP+ (the active metabolite of MPTP)... 

---