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Nathan Goodyear

Toxicity of the spike protein of COVID-19 is a redox shift phenomenon: A novel therapeu... - 0 views

www.sciencedirect.com/...S0891584923005014

COVID19 COVID-19 cancer inflammation SARS-CoV-2 spike proteins COVID spikeopathy

shared by Nathan Goodyear on 01 Sep 23 - No Cached
  • Redox shift is due to Warburg effect and mitochondrial impairment.
  • Redox shift is due to Warburg effect and mitochondrial impairment.
  • Redox shift is due to Warburg effect and mitochondrial impairment.
  • ...88 more annotations...
  • The cytokine storm is a consequence of mitochondrial dysfunction
  • The cytokine storm is a consequence of mitochondrial dysfunction
  • The cytokine storm is a consequence of mitochondrial dysfunction
  • The cytokine storm is a consequence of mitochondrial dysfunction
  • Lipoic acid, Methylene Blue and Chlorine dioxide relieve COVID-19 spike protein toxicity
  • Lipoic acid, Methylene Blue and Chlorine dioxide relieve COVID-19 spike protein toxicity
  • Lipoic acid, Methylene Blue and Chlorine dioxide relieve COVID-19 spike protein toxicity
  • Lipoic acid, Methylene Blue and Chlorine dioxide relieve COVID-19 spike protein toxicity
  • most diseases display a form of anabolism due to mitochondrial impairment
  • most diseases display a form of anabolism due to mitochondrial impairment
  • most diseases display a form of anabolism due to mitochondrial impairment
  • infection by Covid-19 follows a similar pattern
  • chronic inflammation
  • Long-term effects include redox shift and cellular anabolism as a result of the Warburg effect and mitochondrial dysfunction
  • Long-term effects include redox shift and cellular anabolism as a result of the Warburg effect and mitochondrial dysfunction
  • Long-term effects include redox shift and cellular anabolism as a result of the Warburg effect and mitochondrial dysfunction
  • Long-term effects include redox shift and cellular anabolism as a result of the Warburg effect and mitochondrial dysfunction
  • infection by Covid-19 follows a similar pattern
  • unrelenting anabolism leads to the cytokine storm,
  • unrelenting anabolism leads to the cytokine storm,
  • unrelenting anabolism leads to the cytokine storm,
  • chronic inflammation
  • chronic inflammation
  • infection by Covid-19 follows a similar pattern
  • Lipoic acid and Methylene Blue have been shown to enhance the mitochondrial activity, relieve the Warburg effect and increase catabolism
  • Lipoic acid and Methylene Blue have been shown to enhance the mitochondrial activity, relieve the Warburg effect and increase catabolism
  • Lipoic acid and Methylene Blue have been shown to enhance the mitochondrial activity, relieve the Warburg effect and increase catabolism
  • Methylene Blue, Chlorine dioxide and Lipoic acid may help reduce long-term Covid-19 effects by stimulating the catabolism
  • Methylene Blue, Chlorine dioxide and Lipoic acid may help reduce long-term Covid-19 effects by stimulating the catabolism
  • Methylene Blue, Chlorine dioxide and Lipoic acid may help reduce long-term Covid-19 effects by stimulating the catabolism
  • direct consequence of redox iMeBalance, itself a consequence of decreased energy yield by the mitochondria
  • direct consequence of redox iMeBalance, itself a consequence of decreased energy yield by the mitochondria
  • mitochondrial dysfunction and increased levels of lactate, which are important characteristics of metabolic shift and Warburg effect in many diseases
  • mitochondrial dysfunction and increased levels of lactate, which are important characteristics of metabolic shift and Warburg effect in many diseases
  • increased lactate dehydrogenase activity (LDH) was observed in COVID-19 patients
  • increased lactate dehydrogenase activity (LDH) was observed in COVID-19 patients
  • almost every disease presents an increased anabolism
  • almost every disease presents an increased anabolism
  • cell division is the most sophisticated way to release entropy
  • cell division is the most sophisticated way to release entropy
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      Wow
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      Wow
  • transition from catabolism to anabolism is driven by a redox shift
  • transition from catabolism to anabolism is driven by a redox shift
  • viral spike protein binds to ACE2 receptor of the host cell [22,23].
  • redox signaling plays an important role in regulating immune function and inflammation, and disruptions in this signaling can lead to excessive cytokine production and immune system activation
  • Aging is associated with a poor control of the redox balance
  • thiol/disulfide homeostasis
  • reduced extracellular environment in the elderly and the increased susceptibility to Covid-19 infection
  • reduced extracellular environment in the elderly and the increased susceptibility to Covid-19 infection
  • Redox signaling tightly modulates the inflammatory response and oxidative stress has been reported in acute Covid-19
  • People at high risk are the elderly, patients suffering from metabolic syndrome such as obesity, or those suffering from chronic diseases such as cancer or inflammation
  • COVID-19 patients with severe disease have higher levels of oxidative stress markers and lower antioxidant levels
  • oxidative stress can activate the NLRP3 inflammasome, which is a protein complex that plays a key role in the cytokine storm
  • inflammation leads to the formation of ROS and RNS, while redox iMeBalance results in cellular damage, which in turn triggers an inflammatory response
  • persistently elevated mtROS triggers endothelial dysfunction and inflammation, which results in a vicious loop involving ROS, inflammation, and mitochondrial dysfunction
  • Damaged mitochondria releasing ROS induce inflammation via the NLRP3 inflammasome
  • Damaged mitochondria releasing ROS induce inflammation via the NLRP3 inflammasome
  • reduced environment during the cytokine storm
  • IL-2 is highly up-regulated in Covid-19 patients [37], and IL-2 is known to significantly stimulate the generation of NO in patients
  • Nitric acid is also the key mediator of IL-2-induced hypotension and vascular leak syndrome
  • mitochondrial dysfunction has been linked to the pathogenesis of Covid-19
  • mitochondrial dysfunction triggered by SARS-CoV-2 leads to damage to the mitochondria
  • mitochondrial dysfunction triggered by SARS-CoV-2 leads to damage to the mitochondria
  • As catabolism is decreased, entropy is released through anabolism
  • Elevated levels of lactate, a characteristic of the Warburg effect, were also reported in the high-risk Covid-19
  • elevated levels of ventricular lactic acid consistent with oxidative stress
  • A decrease of ΔΨm is implicated in several inflammation-related diseases
  • decrease in ΔΨm in leucocytes from Covid-19 patients
  • vaccinated with RNA or DNA vaccines triggering the synthesis of the viral spike protein in human cells
  • viral reactivation in varicella-zoster virus [55] or hepatitis [56], coagulopathy and resulting stroke and myocarditis following both DNA-based vaccines [57] and RNA-based vaccines
  • Covid-19, mitochondrial impairment
  • characteristic of the Warburg effect is present in almost every disease and appears to be a central feature in most of the hallmarks of cancer
  • inflammation, mitochondrial dysfunction and increased lactate concentrations in the extracellular fluid
  • In Covid-19, like any inflammation, there is a metabolic rewiring where cells rely on glycolysis
  • As the mitochondria are impaired, the infected cell cannot catabolize efficiently. It will release lactic acid in the blood stream
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      Mitochondrial impairment
  • Striking similarities are seen between cancer, Alzheimer's disease and Covid-19, all related to the Warburg effect
  • Cancer, inflammation, Alzheimer's, and Parkinson's diseases share a common peculiarity, the inability of the cell to export entropy outside the body in the harmless form of heat
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      Entropy: lack of order or predictability; gradual decline into disorder.
  • MEB relieves the Warburg effect [87], improves memory [77], is active in the treatment of depressive episodes [79,80] and reduces the importance of ischemic strokes
  • MEB relieves the Warburg effect [87], improves memory [77], is active in the treatment of depressive episodes [79,80] and reduces the importance of ischemic strokes
  • MEB has been shown to inhibit SARS-Cov-2 replication in vitro
  • MEB has been shown to inhibit SARS-Cov-2 replication in vitro
  • It has been shown that Covid-19-patients treated with MEB, have a significant reduction in hospital stay duration and mortality
  • MeB is an acceptor-donor molecule
  • MeB + can take a pair of electrons (of H atoms) and MeBH can release this pair easily, so that MeB is partially recycled like a catalyst
  • MeB acts as an electron bridge between a donor (FADH2, FMNH, NADH) and an acceptor (complex IV of ETC or oxygen itself)
  • As a coenzyme of pyruvate dehydrogenase (PDH), alpha-lipoic acid (ALA) initiates the formation of acetyl-CoA to feed the TCA cycle
  • ALA enhances the catabolism of carbon. cycle and therefore may reduce the Warburg effect and consequently, lactate production
  • Methylene Blue plays a similar role after the TCA cycle, by carrying electrons to complex IV of the electron transport chain
  • Drugs such as lipoic acid and MeB, which target the metabolism, decrease the redox shift by increasing catabolism
Nathan Goodyear

Atorvastatin treatment reduces exercise capac... [J Appl Physiol. 2011] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...21852406

statin mitochondria energy ATP muscle damage performance exercise

shared by Nathan Goodyear on 16 Mar 12 - No Cached
  • Nathan Goodyear on 16 Mar 12
     
    statin therapy damages mitochondria. Mitochondria are the powerhouses of the cell: they are the energy producers of the cell.  It is no surprise that damage to the cells capacity to make energy will in turn decrease the capacity of muscle to perform.
Nathan Goodyear

Oxidative damage to mitochondria and aging. [Exp Gerontol. 2001] - PubMed result - 0 views

www.ncbi.nlm.nih.gov/...11404044

mitochondria damage aging oxidative

shared by Nathan Goodyear on 08 Feb 11 - No Cached
  • Oxidative damage to mitochondria and aging.
  • Nathan Goodyear on 08 Feb 11
     
    mitochondria and aging
Nathan Goodyear

Powering the Cell: Mitochondria « XVIVO - 0 views

www.xvivo.net/powering-the-cell-mitochondria

mitochondria

shared by Nathan Goodyear on 25 Mar 11 - No Cached
  • Nathan Goodyear on 25 Mar 11
     
    Powering the cell: Mitochondria
Nathan Goodyear

Metabolic management of brain cancer - 0 views

www.sciencedirect.com/...S0005272810006857

brain cancer

shared by Nathan Goodyear on 17 Jun 13 - No Cached
  • Glutamine is a major metabolic fuel for both brain tumor cells and tumor-associated macrophages (TAMs)
  • the malignant phenotype of brain tumor cells that survive radiotherapy is often greater than that of the cells from the original tumor.
  • Conventional chemotherapy has faired little better than radiation therapy for the long-term management of malignant brain cancer
  • ...37 more annotations...
  • most conventional radiation and brain cancer chemotherapies can enhance glioma energy metabolism and invasive properties, which would contribute to tumor recurrence and reduced patient survival [34].
  • We contend that all cancer regardless of tissue or cellular origin is a disease of abnormal energy metabolism
  • complex disease phenotypes can be managed through self-organizing networks that display system wide dynamics involving oxidative and non-oxidative (substrate level) phosphorylation
  • As long as brain tumors are provided a physiological environment conducive for their energy needs they will survive; when this environment is restricted or abruptly changed they will either grow slower, growth arrest, or perish [8] and [19]
  • New information also suggests that ketones are toxic to some human tumor cells and that ketones and ketogenic diets might restrict availability of glutamine to tumor cells [68], [69] and [70].
  • The success in dealing with environmental stress and disease is therefore dependent on the integrated action of all cells in the organism
  • Tumor cells survive in hypoxic environments not because they have inherited genes making them more fit or adaptable than normal cells, but because they have damaged mitochondria and have thus acquired the ability to derive energy largely through substrate level phosphorylation
  • Cancer cells survive and multiply only in physiological environments that provide fuels (mostly glucose and glutamine) subserving their requirement for substrate level phosphorylation
  • Integrity of the inner mitochondrial membrane is necessary for ketone body metabolism since β-hydroxybutyrate dehydrogenase, which catalyzes the first step in the metabolism of β-OHB to acetoacetate, interacts with cardiolipin and other phospholipids in the inner membrane
  • the mitochondria of many gliomas and most tumors for that matter are dysfunctional
  • Cardiolipin is essential for efficient oxidative energy production and mitochondrial function
  • Any genetic or environmental alteration in the content or composition of cardiolipin will compromise energy production through oxidative phosphorylation
  • The Crabtree effect involves the inhibition of respiration by high levels of glucose
  • the Warburg effect involves elevated glycolysis from impaired oxidative phosphorylation
  • the Crabtree effect can be reversible, the Warburg effect is largely irreversible because its origin is with permanently damaged mitochondria
  • The continued production of lactic acid in the presence of oxygen is the metabolic hallmark of most cancers and is referred to as aerobic glycolysis or the Warburg effect
  • We recently described how the retrograde signaling system could induce changes in oncogenes and tumor suppressor genes to facilitate tumor cell survival following mitochondrial damage [48].
  • In addition to glycolysis, glutamine can also increase ATP production under hypoxic conditions through substrate level phosphorylation in the TCA cycle after its metabolism to α-ketoglutarate
  • mitochondrial lipid abnormalities, which alter electron transport activities, can account in large part for the Warburg effect
  • targeting both glucose and glutamine metabolism could be effective for managing most cancers including brain cancer
  • The bulk of experimental evidence indicates that mitochondria are dysfunctional in tumors and incapable of generating sufficient ATP through oxidative phosphorylation
  • Cardiolipin defects in tumor cells are also associated with reduced activities of several enzymes of the mitochondrial electron transport chain making it unlikely that tumor cells with cardiolipin abnormalities can generate adequate energy through oxidative phosphorylation
  • The Crabtree effect involves the inhibition of respiration by high levels of glucose
  • Warburg effect involves elevated glycolysis from impaired oxidative phosphorylation
  • TCA cycle substrate level phosphorylation could therefore become another source of ATP production in tumor cells with impairments in oxidative phosphorylation
  • Caloric restriction, which lowers glucose and elevates ketone bodies [63] and [64], improves mitochondrial respiratory function and glutathione redox state in normal cells
  • DR naturally inhibits glycolysis and tumor growth by lowering circulating glucose levels, while at the same time, enhancing the health and vitality of normal cells and tissues through ketone body metabolism
  • DR is anti-angiogenic
  • DR also reduces angiogenesis in prostate and breast cancer
  • We suggest that apoptosis resistance arises largely from enhanced substrate level phosphorylation of tumor cells and to the genes associated with elevated glycolysis and glutaminolysis, e.g., c-Myc, Hif-1a, etc, which inhibit apoptosis
  • Modern medicine has not looked favorably on diet therapies for managing complex diseases especially when well-established procedures for acceptable clinical practice are available, regardless of how ineffective these procedures might be in managing the disease
  • More than 60 years of clinical research indicates that such approaches are largely ineffective in extending survival or improving quality of life
  • The process is rooted in the well-established scientific principle that tumor cells are largely dependent on substrate level phosphorylation for their survival and growth
  • Glucose and glutamine drive substrate level phosphorylation
  • targeting the glycolytically active tumor cells that produce pro-cachexia molecules, restricted diet therapies can potentially reduce tumor cachexia
  • It is important to recognize, however, that “more is not better” with respect to the ketogenic diet
  • Blood glucose ranges between 3.0 and 3.5 mM (55–65 mg/dl) and β-OHB ranges between 4 and 7 mM should be effective for tumor management
  • Nathan Goodyear on 17 Jun 13
     
    Dr Seyfriend presents his metabolic approach to the treatment of brain cancer.
Nathan Goodyear

Early long-term L-T3 replacement rescues mitochondria and prevents ischemic cardiac rem... - 0 views

onlinelibrary.wiley.com/...abstract

T3 thyroid hormone hormones MI mitochondria HIF-1alpha

shared by Nathan Goodyear on 29 Jun 13 - No Cached
  • Nathan Goodyear on 29 Jun 13
     
    T3 in the post MI individual decreases the MI infarct size and the progression to heart failure. What is really  interesting about this study is that the T3 induced mitochondrial biogenesis and activity which is a great thing in recovery of MI and also in disease i.e. cancer.  However, it appears to increase HIF-1alpha and angiogenesis which is stimulated by retrograde signaling.  There is a muddied picture here.  Because T3 stimulates oxidative phosphorylation and mitochondria biogenesis which is favorable for health.  However, in this study of rats, it induced HIF-1alpha and angiogenesis in post MI, which is favorable to recovery, yet this is unfavorable for cancer.    Yet oxidative phosphorylation is favorable to cancer prevention/elimination and MI recovery.
Nathan Goodyear

Classification of mitocans, anti-cancer drugs acting on mitochondria - 0 views

www.medicinalgenomics.com/...MitoCan.pdf

cancer mitochondria 3-bromopyruvate 3-BrPA

shared by Nathan Goodyear on 11 Sep 13 - No Cached
  • Nathan Goodyear on 11 Sep 13
     
    Good review of therapies directed at mitochondria in cancer.
Nathan Goodyear

Mitochondria in the diabetic heart. [Cardiovasc Res. 2010] - PubMed result - 0 views

www.ncbi.nlm.nih.gov/...20639213

mitochondria heart disease diabetes

shared by Nathan Goodyear on 14 Jan 11 - No Cached
  • abnormalities in cardiomyocyte mitochondrial energetics appear to contribute substantially to the development of cardiac dysfunction in diabetes
  • Nathan Goodyear on 14 Jan 11
     
    Mitochondria in the diabetic heart.
Nathan Goodyear

Mitochondria, oxidative stress and aging. [Free Radic Res. 2000] - PubMed result - 0 views

www.ncbi.nlm.nih.gov/...10730818

stress mitochondria oxidative aging

shared by Nathan Goodyear on 08 Feb 11 - No Cached
  • mitochondrial aging may be prevented by antioxidants.
  • Nathan Goodyear on 08 Feb 11
     
    antioxidants protect mitochondria oxidative stress and slow aging
Nathan Goodyear

Alcohol and mitochondria: a dysfunctional relation... [Gastroenterology. 2002] - PubMed... - 0 views

www.ncbi.nlm.nih.gov/...12055609

mitochondria alcohol

shared by Nathan Goodyear on 08 Feb 11 - No Cached
  • Nathan Goodyear on 08 Feb 11
     
    excess alcohol and mitochondria don't mix
Nathan Goodyear

Mitochondria and neurodegeneration. [Biosci Rep. 2007] - PubMed result - 0 views

www.ncbi.nlm.nih.gov/...17486441

mitochondria neurodegeneration

shared by Nathan Goodyear on 07 Feb 11 - No Cached
  • Nathan Goodyear on 07 Feb 11
     
    mitochondria dysfunction and contribution to neurodegenerative disease
Nathan Goodyear

Mitochondria: Gateway for Cytoprotection -- Dzeja et al. 89 (9): 744 -- Circulation Res... - 0 views

circres.ahajournals.org/...744

mitochondria energy

shared by Nathan Goodyear on 03 Mar 11 - No Cached
  • Nathan Goodyear on 03 Mar 11
     
    mitochondria have emerged as gateways responsible for launching and coordinating cellular protective programs
Nathan Goodyear

Cellular Respiration - 0 views

users.rcn.com/...CellularRespiration.html

mitochondria biology

shared by Nathan Goodyear on 25 Mar 11 - Cached
  • Nathan Goodyear on 25 Mar 11
     
    mitochondria
Nathan Goodyear

mitochondria - 0 views

www.johnkyrk.com/mitochondrion.html

mitochondria

shared by Nathan Goodyear on 25 Mar 11 - Cached
  • Nathan Goodyear on 25 Mar 11
     
    Good animation of mitochondria and energy production
Nathan Goodyear

The critical role of glutathione in maintenance of the mitochondria... - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...20888410

glutathione GSH mitochondria detoxification

shared by Nathan Goodyear on 11 Nov 14 - No Cached
  • Nathan Goodyear on 11 Nov 14
     
    Abstract only available in this link--loss of glutathione results in decreased mitochondria.  This has significant disease implications.
Nathan Goodyear

Mitochondria and Cancer - 0 views

www.ncbi.nlm.nih.gov/...PMC4779192

cancer mitochondria

shared by Nathan Goodyear on 05 Oct 18 - No Cached
  • aerobic glycolysis
  • aerobic glycolysis
  • the “Warburg effect” is the basis for tumor imaging by FDG-PET
  • ...1 more annotation...
  • In most cancers, oncogenic driver mutations such as activation of K-ras, c-Myc and phosphatidylinositol-3 (PI3) kinase or loss of phosphatase and tensin homolog (Pten) and p53, not mutations that inactivate mitochondrial respiration complexes, promote glycolysis
  • Nathan Goodyear on 05 Oct 18
     
    great read on mitochondria and cancer.
Nathan Goodyear

Succinate Dehydrogenase Supports Metabolic Repurposing of Mitochondria to Drive Inflamm... - 0 views

www.cell.com/...S0092-8674(16)31162-X

inflammation LPS macrophages lipopolysaccharide mitochondria energy ATP ROS

shared by Nathan Goodyear on 12 Oct 16 - No Cached
  • Nathan Goodyear on 12 Oct 16
     
    Fascinating study: inflammation via LPS induces pro-inflammatory move by macrophages that induces a change in mitochondria to increase inflammation and decrease ATP production.
Nathan Goodyear

Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer - 0 views

www.ncbi.nlm.nih.gov/...PMC2567082

cancer dichloroacetate dichloracetic acid DCA

shared by Nathan Goodyear on 07 Nov 18 - No Cached
  • The generic drug dichloroacetate is an orally available small molecule that, by inhibiting the pyruvate dehydrogenase kinase, increases the flux of pyruvate into the mitochondria, promoting glucose oxidation over glycolysis
  • The most important reason for the poor performance of cancer drugs is the remarkable heterogeneity and adaptability of cancer cells. The molecular characteristics of histologically identical cancers are often dissimilar and molecular heterogeneity frequently exists within a single tumour.
  • Because GO is far more efficient in generating ATP compared with GLY (producing 36 vs 2 ATP per glucose
  • ...9 more annotations...
  • molecule), cancer cells upregulate glucose receptors and significantly increase glucose uptake in an attempt to ‘catch up
  • early carcinogenesis often occurs in a hypoxic microenvironment, the transformed cells have to rely on anaerobic GLY for energy production.
  • Hypoxia-inducible factor (HIF) is activated in hypoxic conditions
  • evidence suggests that transformation to a glycolytic phenotype offers resistance to apoptosis
  • non-small cell lung cancer, breast cancer and glioblastoma
  • Dichloroacetate activated the pyruvate dehydrogenase, which resulted in increased delivery of pyruvate into the mitochondria
  • DCA increased GO and depolarised the mitochondria, returning the membrane potential towards the levels of the non-cancer cells, without affecting the mitochondria of non-cancerous cells
  • induction of apoptosis by DCA in non-small cell lung cancer, breast cancer and glioblastoma cell lines
  • DCA was shown to induce apoptosis in endometrial (Wong et al, 2008) and prostate (Cao et al, 2008) cancer cells
  • Nathan Goodyear on 07 Nov 18
     
    DCA as targeted therapy in cancer.
Nathan Goodyear

The Single Nucleotide Polymorphism Gly482Ser in the PGC-1α Gene Impairs Exerc... - 0 views

journals.plos.org/...article

epigenetics exercise training muscle SNPs PGC-1alpha

shared by Nathan Goodyear on 30 Nov 17 - No Cached
  • Oxidative slow-twitch type I fibres (henceforth briefly called ‘slow fibres’) contain MHC-Iβ. They use oxidative phosphorylation (OXPHOS) to generate ATP and are thus highly fatigue resistant and preferentially activated during endurance exercise. Slow fibres comprise high amounts of mitochondria, myoglobin and lipid droplets, and are well supplied by capillaries
  • there are three types of fast-twitch fibres (types IIA, IID/X, IIB, with the corresponding MHC isoforms IIa, IId/x, IIb) which are all used for rapid high-force generation. Oxidative-glycolytic fast-twitch type IIA fibres have intermediate amounts of mitochondria, lipid droplets and capillaries, and are intermediately resistant to fatigue (as compared to type I and types IIB and IID/X). Glycolytic fast-twitch type IID/X fibres are poor in mitochondria, lipids and capillaries and more susceptible to fatique than type IIA. Glycolytic fast-twitch type IIB fibres have the lowest amounts of mitochondria, lipid droplets and capillaries, but generate the highest contraction velocities
  • Several studies have shown that PGC-1α is upregulated after endurance training
  • ...3 more annotations...
  • upregulation of PGC-1α expression enhances and/or maintains mitochondrial biogenesis, eventually leading to an increased mitochondrial content of the muscle fibres.
  • PGC-1α also plays an important role in the pathogenesis of insulin resistance and T2D
  • carriers of the Gly482Ser SNP have a reduced cardiorespiratory fitness and a higher risk for metabolic syndrome and T2D
  • Nathan Goodyear on 30 Nov 17
     
    Those that carry the risk SNP for Gly482Ser for the PGC-1alpha gene dont' transform type II to type I and thus decrease the effectiveness of aeorbic exercise training, decreased oxidative phosphorylation, decreased lipid oxidation, increased lipid accumulaiton in muscle, and increased risk of IR, obesity, and diabetes.
Nathan Goodyear

American College of Cardiology Foundation | Journal of the American College of Cardiolo... - 0 views

content.onlinejacc.org/article.aspx

mitochondria oxidative stress heart failure heart

shared by Nathan Goodyear on 19 Mar 13 - No Cached
  • Although currently no drugs that specifically target mitochondrial biogenesis in HF are available, acceleration of this process through adenosine monophosphate–activated kinase (AMPK), endothelial nitric oxide synthase (eNOS), and other pathways may represent a promising therapeutic approach
  • Mitochondrial biogenesis can be enhanced therapeutically with the use of adenosine monophosphate kinase (AMPK) agonists, stimulants of nitric oxide/cyclic guanosine monophosphate (NO/cGMP) pathway (including phosphodiesteraes type 5 inhibitors), or resveratrol
  • metformin, a commonly used antidiabetic drug that activates AMPK signaling
  • ...10 more annotations...
  • Recent evidence suggests that the eNOS/NO/cGMP pathway is an important activator of mitochondrial biogenesis
  • BH4 (tetrahydrobiopterin) supplementation can prevent eNOS uncoupling and was found to reduce left ventricular hypertrophy
  • folic acid is known to replenish reduced BH4 and has been shown to protect the heart through increased eNOS activity
  • Both folate deficiency and inhibition of BH4 synthesis were associated with reduced mitochondrial number and function
  • Resveratrol, a polyphenol compound responsible for the cardioprotective properties of red wine, was recently identified as a potent stimulator of mitochondrial biogenesis
  • epidemiological studies reveal a reduced risk of cardiovascular disease in premenopausal, but not post-menopausal, women compared with men
  • post-menopausal women
    • Nathan Goodyear
      Nathan Goodyear on 19 Mar 13
       
      I would hypothesis that a change in the predominance of ER expression is one of ER beta to ER alpha: creating a more pro-inflammatory signal.
  • The majority of ROS in the heart appear to come from uncoupling of mitochondrial electron transport chain at the level of complexes I and III
  • Because the majority of ROS in HF comes from mitochondria, these organelles are the primary target of oxidative damage.
  • cardioprotective therapies such as angiotensin-converting enzyme inhibitors and ATII receptor blockers were shown to possess antioxidant properties, although it is not known whether they target mitochondrial ROS directly or indirectly
  • Nathan Goodyear on 19 Mar 13
     
    great review of mitochondrial biogenesis, oxidative stress and heart failure.  
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