Anti-aging effects of deuterium depletion on Mn-induced toxicity in a C. elegans model

Ávila, Daiana Silva; Somlyai, Gábor; Somlyai, Ildikó; Aschner, Michael

doi:10.1016/j.toxlet.2012.04.014

Cited by 43 publications

(44 citation statements)

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“…Forth way is to target hydrogen bond network of cancer signaling by the proton beam radiation disrupting a hydrogen bond network and causing apoptosis of cancer cells. However, robustness and stability of the cancer system could be targeted by the simultaneous targeting of the redox balance change [Radisavljevic, 2008] and hydrogen balance change [Somlyai et al, 2010;Tong et al, 2011;Avila et al, 2012; Guitart et al, 2017], or proton beam radiation [Marshall et al, 2016] and/or with nitric oxide balance change [Radisavljevic, 2003] all leading to apoptosis of the cancer cells, but in this case there is always a risk for failure of the entire living system too, instead of rather slow then fast apoptosis of cancer cells by slow conversion of the positive feedback loops and slow disappearance of cancer malignant phenotype [Radisavljevic, 2003[Radisavljevic, , 2004a[Radisavljevic, ,b, 2008[Radisavljevic, , 2013a[Radisavljevic, ,b,c, 2015a[Radisavljevic, ,b, 2016. …”

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confidence: 99%

AKT as Locus of Hydrogen Bond Network in Cancer

Radisavljevic

2017

J of Cellular Biochemistry

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Generation and maintenance of a cancer complexity and robustness are impossible without hydrogen element. It is essential element for the cancer signaling through the AKT locus. Hyperactivated AKT locus by a positive feedback loops from the cancer hypoxic microenvironment generates a hydrogen bond network. Such network initiates protein-protein interaction at the AKT active site and at the same time stabilizes signal propagation. A hydrogen bond network conforms an entropy/enthalpy energetic process used for the interconversion of the AKT protein in metastasis formation and maintenance. Targeting the AKT locus by the redox balance change or hydrogen balance change or proton beam radiation disrupts a hydrogen bond network leading to the disappearance of a cancer complexity and robustness causing failure of the complex energy system in solid cancers and hematological malignancy. J. Cell. Biochem. 119: 130-133, 2018. © 2017 Wiley Periodicals, Inc. KEY WORDS: HYDROGEN BOND NETWORK; AKT LOCUS; CANCER SIGNALING; CANCER ROBUSTNESS AND COMPLEXITYI nitiation of signaling begins at active site of interacting proteins by a hydrogen bonds conformation. However, propagation of signals is achieved by the hydrogen bond stabilization at the active site. Thus, signal transduction network generation and propagation relay on hydrogen bonds. Hydrogen is essential element in cancer signaling. AKT as a locus of cancer robustness and fragility [Radisavljevic, 2004a[Radisavljevic, , b, 2008[Radisavljevic, , 2013a[Radisavljevic, ,b,c, 2015a[Radisavljevic, ,b, 2016 functions trough the hydrogen bonds. Targeting hydrogen bond as a specific element in signaling could be achieved by the hydrogen balance change which will cause complete failure of cancer robustness and complexity. Network of the complex signaling pathways for cancer cell proliferation through the Rb/AKT/NO pathway [Radisavljevic, 2004b] and the PI3 K/AKT/mTOR/ RAN pathway [Radisavljevic and Gonzalez-Flecha, 2004], cell migration through the VEGF/AKT/ICAM1 pathway [Radisavljevic et al., 2000] are achieved by the hydrogen bonds at active sites [Ishikita and Saito, 2013;Liu et al., 2015] of the AKT locus [Radisavljevic et al., 2000;Radisavljevic, 2004a Radisavljevic, ,b, 2008Radisavljevic, , 2013a Radisavljevic, ,b,c, 2015a Radisavljevic, ,b, 2016Radisavljevic and Gonzalez-Flecha, 2004]. AKT LOCUS OF HYDROGEN BOND NETWORKS IN CANCER ROBUSTNESS AND FRAGILITYHydrogen molecule is essential for a living cell function. Such function is a cell signaling which involves protein interactions. Hydrogen bonds are essential in the protein-protein interaction making a hydrogen bond networks and cell energetics crucial in the protein conformation change [Ishikita and Saito, 2013]. Initiation of signaling, stabilization, and propagation of signals in a cancer hypoxic microenviroment is crucial for the interacting proteins [Radisavljevic, 2004a[Radisavljevic, ,b, 2008[Radisavljevic, , 2013a[Radisavljevic, ,b,c, 2015a[Radisavljevic, ,b, 2016. Protein-protein interaction occ...

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confidence: 99%

AKT as Locus of Hydrogen Bond Network in Cancer

Radisavljevic

2017

J of Cellular Biochemistry

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“…Both effects are highly reproducible in C. elegans. Increased expression of Akt was also observed in worms exposed to Mn (Avila et al 2012b). …”

Section: Introductionmentioning

confidence: 91%

Role of Caenorhabditis elegans AKT-1/2 and SGK-1 in Manganese Toxicity

et al. 2018

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Excessive levels of the essential metal manganese (Mn) may cause a syndrome similar to Parkinson's disease. The model organism Caenorhabditis elegans mimics some of Mn effects in mammals, including dopaminergic neurodegeneration, oxidative stress, and increased levels of AKT. The evolutionarily conserved insulin/insulin-like growth factor-1 signaling pathway (IIS) modulates worm longevity, metabolism, and antioxidant responses by antagonizing the transcription factors DAF-16/FOXO and SKN-1/Nrf-2. AKT-1, AKT-2, and SGK-1 act upstream of these transcription factors. To study the role of these proteins in C. elegans response to Mn intoxication, wild-type N2 and loss-of-function mutants were exposed to Mn (2.5 to 100 mM) for 1 h at the L1 larval stage. Strains with loss-of-function in akt-1, akt-2, and sgk-1 had higher resistance to Mn compared to N2 in the survival test. All strains tested accumulated Mn similarly, as shown by ICP-MS. DAF-16 nuclear translocation was observed by fluorescence microscopy in WT and loss-of-function strains exposed to Mn. qRT-PCR data indicate increased expression of γ-glutamyl cysteine synthetase (GCS-1) antioxidant enzyme in akt-1 mutants. The expression of sod-3 (superoxide dismutase homologue) was increased in the akt-1 mutant worms, independent of Mn treatment. However, dopaminergic neurons degenerated even in the more resistant strains. Dopaminergic function was evaluated with the basal slowing response behavioral test and dopaminergic neuron integrity was evaluated using worms expressing green fluorescent protein (GFP) under the dopamine transporter (DAT-1) promoter. These results suggest that AKT-1/2 and SGK-1 play a role in C. elegans response to Mn intoxication. However, tissue-specific responses may occur in dopaminergic neurons, contributing to degeneration.

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“…It was also noted the positive impact of DDW on indicators of saturation the liver tissue by oxygen: the observed increase in pO 2 was ∼15%, i.e., cell respiration increased 1,3 times [38]. On beneficial effect on health of experimental mice evidenced the increased resistance and weight increase compared with the control group [39]. It was also indicated that DDW increases the rate of metabolic reactions.…”

Section: Clinical Evidence On the Benefits Of Deuterium Depleted Watementioning

confidence: 99%

Multifactorial Research of Longevity Phenomenon in Mountainous and Field Areas of Bulgaria

Ignatov¹,

Mosin²,

Velikov³

et al. 2015

Russian Journal of Biological Research

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The article outlines the data on longevity factors and mountain water in factorial research of phenomenon of longevity in mountainous and field areas of Bulgaria. It was established the dependence among various internal and external factors on a phenomenon of longevity -the residence area, health status, gender and heredity. Natural waters derived from various Bulgarian water springs as well as water with varying deuterium content and the human blood serum of cancer patients were investigated by IR, NES and DNES methods. As estimation factor was measured the values of the average energy of hydrogen bonds (∆E H...O) among H2O molecules, as well as local maxima in the IR, and DNES-spectra of various samples of water and human blood serum at ∆EH...O = -0,1387 eV (the DNES-method) and λ = 8,95 μm (the IR-method). The increased content of deuterium in water leads to physiological, morphological and cytology alterations of the cell, and also renders negative influence on cellular metabolism, while deuterium depleted water with the reduced deuterium content until the deep removal of deuterium (60-100 ppm) has 124Russian Journal of Biological Research, 2015, Vol. (5), Is. 3 beneficial effects on human health. For a group of people in critical condition of life and patients with malignant tumors the greatest values of local maxima in DNES-spectra are shifted to lower energies relative to the control group.Keywords: deuterium, heavy water, deuterium depleted water, longevity, mountain water, IR, NES, DNES. IntroductionThe question of longevity has always been an exciting one for humanity. Aging is a biological process, which leads to reduction of the vital functions of the body, limiting its adaptive capacities, and development of age-related pathologies and ultimately increasing the likelihood of death, is a part of the normal ontogeny and is caused by the same processes that lead to increased functional activity of various body systems in earlier periods of life. It is possible that these processes along with other processes (growth and development of the organism, etc.) are programmed in the human genome and biological mechanism of regulation. The question to what extent aging is dependent on heredity is not sufficiently proven in modern science.Like other biological processes, aging is accelerated under the influence of certain exogenous and endogenous factors and occurs in different individuals with different speed, which depends on genetic differences and environmental factors. The best chance for longevity gives the longevity of immediate direct genetic ancestors. That is why the direct descendants of centenarians generally have the best chances for longevity. O. Burger demonstrated that life expectancy has increased substantially from the 19 th to the 20 th century and that this cannot be advantageously associated with the human genome [1]. The main factors of longevity are water quality, food and improved advancement of medicine. For example, in Bulgaria the average life expectancy from 1935 to 1939 wa...

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Anti-aging effects of deuterium depletion on Mn-induced toxicity in a C. elegans model

Cited by 43 publications

References 34 publications

AKT as Locus of Hydrogen Bond Network in Cancer

AKT as Locus of Hydrogen Bond Network in Cancer

Role of Caenorhabditis elegans AKT-1/2 and SGK-1 in Manganese Toxicity

Multifactorial Research of Longevity Phenomenon in Mountainous and Field Areas of Bulgaria

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