Alpha-lipoic acid does not alter stress protein response to acute exercise in diabetic brain

2010 ◽  
Vol 28 (8) ◽  
pp. 644-650 ◽  
Author(s):  
Jani Lappalainen ◽  
Zekine Lappalainen ◽  
Niku K. J. Oksala ◽  
David E. Laaksonen ◽  
Savita Khanna ◽  
...  
Keyword(s):  
Lipoic Acid ◽  
Acute Exercise ◽  
Stress Protein ◽  
Alpha Lipoic Acid ◽  
Diabetic Brain ◽  
Protein Response

Acute Exercise and Thioredoxin-1 in Rat Brain, and Alpha-Lipoic Acid and Thioredoxin-Interacting Protein Response, in Diabetes

2010 ◽  
Vol 20 (3) ◽  
pp. 206-215 ◽  
Author(s):  
Zekine Lappalainen ◽  
Jani Lappalainen ◽  
David E. Laaksonen ◽  
Niku K.J Oksala ◽  
Savita Khanna ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipoic Acid ◽  
Acute Exercise ◽  
Exhaustive Exercise ◽  
Favorable Effect ◽  
Alpha Lipoic Acid ◽  
Interacting Protein ◽  
Protein Response ◽  
Response To Exercise ◽  
The Brain

Thioredoxin (TRX) is a protein disulfide reductase that plays an important role in many thiol-dependent cellular reductive processes, antioxidant protection, and signal transduction. Moreover, TRX reduces and maintains the function of many proteins during oxidative stress, which is increased in diabetes. The authors recently reported that diabetes impairs brain redox status and TRX response to exercise training. As a continuation of their studies, they hypothesized that alpha-lipoic acid, a natural thiol antioxidant, has a favorable effect on the brain TRX and glutathione (GSH) system in diabetes. Streptozotocin-induced diabetes was used as a chronic model and exhaustive exercise as an acute model for disrupted redox balance. Half the diabetic and nondiabetic animals were subjected to a bout of exhaustive exercise after 8 wk with or without lipoic acid and analyzed for key thiol antioxidants. Lipoic acid neither altered diabetes-induced oxidative stress as assessed by the increased ratio of oxidized to total GSH nor had any impact on the antioxidant protein response to exercise. However, lipoic acid increased mRNA of TRX-interacting protein, an inhibitor of TRX-1, and glutaredoxin-1 in diabetes. Exercise increased TRX-1 mRNA in both diabetic and nondiabetic animals but had no effect on TRX-1 protein. Cytosolic superoxide dismutase mRNA was only increased in diabetes, whereas exercise increased the protein levels in nondiabetic animals. The findings suggest that exhaustive exercise induces mRNA of TRX-1 in the brain and that lipoic acid cannot prevent diabetes-induced disturbances in GSH homeostasis. Because lipoic acid increased TRX-interacting protein transcription in diabetes, high doses may impair TRX-1 homeostasis.

Age and dose-dependent effects of alpha-lipoic acid on human microtubule-associated protein tau-induced endoplasmic reticulum unfolded protein response: implications for Alzheimer’s disease

2020 ◽  
Author(s):  
Elahe Zarini-Gakiye ◽  
Nima Sanadgol ◽  
Kazem Parivar ◽  
Gholamhassan Vaezi
Keyword(s):  
Endoplasmic Reticulum ◽  
Unfolded Protein Response ◽  
Lipoic Acid ◽  
Alpha Lipoic Acid ◽  
Protein Patterns ◽  
Locomotor Function ◽  
Protein Tau ◽  
Microtubule Associated Protein Tau ◽  
Unfolded Protein ◽  
Protein Response

AbstractBackgroundIn human tauopathies, pathological aggregation of misfolded/unfolded proteins particularly microtubule-associated protein tau (MAPT, tau) is considered to be essential mechanisms that trigger the induction of endoplasmic reticulum (ER) stress. Here we assessed the molecular effects of natural antioxidant alpha-lipoic acid (ALA) in human tauR406W (htau)-induced ER unfolded protein response (ERUPR) in the young and older flies.MethodsIn order to reduce htau neurotoxicity during brain development, we used a transgenic model of tauopathy where the maximum toxicity was observed in adult flies. Then, the effects of ALA (0.001, 0.005, and 0.025% w/w of diet) in htau-induced ERUPR in the ages 20 and 30 days were evaluated.ResultsData from expression (mRNA and protein) patterns of htau, analysis of eyes external morphology as well as larvae olfactory memory were confirmed our tauopathy model. Moreover, expression of ERUPR-related proteins involving activating transcription factor 6 (ATF6), inositol regulating enzyme 1 (IRE1), and protein kinase RNA-like ER kinase (PERK) were upregulated and locomotor function decreased in both ages of the model flies. Remarkably, the lower dose of ALA modified ERUPR and supported the reduction of behavioral deficits in youngest adults through enhancement of GRP87/Bip, reduction of ATF6, downregulation of PERK-ATF4 pathway, and activation of the IRE1-XBP1 pathway. On the other hand, only a higher dose of ALA was able to affect the ERUPR via moderation of PERK-ATF4 signaling in the oldest adults. As ALA exerts their higher protective effects on the locomotor function of younger adults when htauR406W expressed in all neurons (htau-elav) and mushroom body neurons (htau-ok), we proposed that ALA has age-dependent effects in this model.ConclusionTaken together, based on our results we conclude that aging potentially influences the ALA effective dose and mechanism of action on tau-induced ERUPR. Further molecular studies will warrant possible therapeutic applications of ALA in age-related tauopathies.

scholarly journals Exercise and Redox Status Responses Following Alpha-Lipoic Acid Supplementation in G6PD Deficient Individuals

Antioxidants ◽  
2018 ◽  
Vol 7 (11) ◽  
pp. 162 ◽  
Author(s):  
Kalliopi Georgakouli ◽  
Ioannis Fatouros ◽  
Apostolos Fragkos ◽  
Theofanis Tzatzakis ◽  
Chariklia Deli ◽  
...  
Keyword(s):  
Uric Acid ◽  
Lipoic Acid ◽  
G6pd Deficiency ◽  
Acute Exercise ◽  
Thiobarbituric Acid ◽  
Redox Balance ◽  
Redox Status ◽  
Protein Carbonyls ◽  
Alpha Lipoic Acid ◽  
Double Blind

G6PD deficiency renders cells more susceptible to oxidative insults, while antioxidant dietary supplementation could restore redox balance and ameliorate exercise-induced oxidative stress. To examine the effects of alpha-lipoic acid (ALA) supplementation on redox status indices in G6PD deficient individuals, eight male adults with G6PD deficiency (D) participated in this randomized double-blind placebo-controlled crossover trial. Participants were randomly assigned to receive ALA (600 mg/day) or placebo for 4 weeks separated by a 4-week washout period. Before and at the end of each treatment period, participants exercised following an exhaustive treadmill exercise protocol. Blood samples were obtained before (at rest), immediately after and 1h after exercise for later analysis of total antioxidant capacity (TAC), uric acid, bilirubin, thiobarbituric acid reactive substances (TBARS) and protein carbonyls (PC). ALA resulted in significantly increased resting TAC and bilirubin concentrations. Moreover, TAC increased immediately and 1h after exercise following both treatment periods, whereas bilirubin increased immediately after and 1h after exercise following only ALA. No significant change in uric acid, TBARS or PC was observed at any time point. ALA supplementation for 4 weeks may enhance antioxidant status in G6PD individuals; however, it does not affect redox responses to acute exercise until exhaustion or exercise performance.

scholarly journals Age and Dose-dependent Effects of Alpha-lipoic Acid on Human Microtubule-associated Protein Tau-induced Endoplasmic Reticulum Unfolded Protein Response: Implications for Alzheimer’s Disease

2021 ◽  
Vol 20 ◽  
Author(s):  
Elahe Zarini-Gakiye ◽  
Nima Sanadgol ◽  
Kazem Parivar ◽  
Gholamhassan Vaezi
Keyword(s):  
Endoplasmic Reticulum ◽  
Unfolded Protein Response ◽  
Lipoic Acid ◽  
Alpha Lipoic Acid ◽  
Protein Patterns ◽  
Locomotor Function ◽  
Protein Tau ◽  
Microtubule Associated Protein Tau ◽  
Unfolded Protein ◽  
Protein Response

Background: In human tauopathies, pathological aggregation of misfolded/unfolded proteins particularly microtubule-associated protein tau (MAPT, tau) is considered to be essential mechanisms that trigger the induction of endoplasmic reticulum (ER) stress. Objective: Here we assessed the molecular effects of natural antioxidant alpha-lipoic acid (ALA) in human tauR406W (htau)-induced ER unfolded protein response (ERUPR) in fruit flies. Methods: In order to reduce htau neurotoxicity during brain development, we used a transgenic model of tauopathy where the maximum toxicity was observed in adult flies. Then, the effects of ALA (0.001, 0.005, and 0.025% w/w of diet) in htau-induced ERUPR and behavioral dysfunctions in the ages 20 and 30 days were evaluated in Drosophila melanogaster. Results: Data from expression (mRNA and protein) patterns of htau, analysis of eyes external morphology as well as larvae olfactory memory were confirmed our tauopathy model. Moreover, expression of ERUPR-related proteins involving activating transcription factor 6 (ATF6), inositol regulating enzyme 1 (IRE1), and protein kinase RNA-like ER kinase (PERK) were upregulated and locomotor function decreased in both ages of the model flies. Remarkably, the lower dose of ALA modified ERUPR and supported the reduction of behavioral deficits in youngest adults through enhancement of GRP87/Bip, reduction of ATF6, downregulation of PERK-ATF4 pathway, and activation of the IRE1-XBP1 pathway. On the other hand, only a higher dose of ALA was able to affect the ERUPR via moderation of PERK-ATF4 signaling in the oldest adults. As ALA also exerts their higher protective effects on the locomotor function of younger adults when htauR406W expressed in all neurons (htau-elav) and mushroom body neurons (htau-ok), we proposed that ALA has age-dependent effects in this model. Conclusion: Taken together, based on our results we conclude that aging potentially influences the ALA effective dose and mechanism of action on tau-induced ERUPR. Further molecular studies will warrant possible therapeutic applications of ALA in age-related tauopathies.

Effect of the alpha-lipoic acid on apoptosis in HIT-T15 cells induced by high glucose

2010 ◽  
Vol 34 (8) ◽  
pp. S14-S14
Author(s):  
Yi Yang ◽  
Wei‑Ping Wang ◽  
Yi‑Nan Liu ◽  
Ting Guo ◽  
Ping Chen ◽  
...  
Keyword(s):  
Lipoic Acid ◽  
High Glucose ◽  
Alpha Lipoic Acid

Evaluation of dissolution profiles of alpha lipoic acid soft gelatin capsules and tablets

Planta Medica ◽  
2011 ◽  
Vol 77 (12) ◽  
Author(s):  
A Uzunovic ◽  
S Hadzidedic ◽  
A Elezovic ◽  
S Pilipovic ◽  
A Sapcanin
Keyword(s):  
Lipoic Acid ◽  
Alpha Lipoic Acid ◽  
Gelatin Capsules ◽  
Soft Gelatin Capsules

Secunder prevention with alpha-lipoic acid and vitamin E in porphyria cutanea tarda patients

2008 ◽  
Vol 46 (05) ◽  
Author(s):  
E Székely ◽  
K Szentmihályi ◽  
M Bor ◽  
Á Pusztai ◽  
T Kurucz ◽  
...  
Keyword(s):  
Vitamin E ◽  
Lipoic Acid ◽  
Porphyria Cutanea Tarda ◽  
Alpha Lipoic Acid

Advanced glycation end product-induced activation of NF-kappaB is suppressed by alpha-lipoic acid in cultured endothelial cells

Diabetes ◽  
1997 ◽  
Vol 46 (9) ◽  
pp. 1481-1490 ◽  
Author(s):  
A. Bierhaus ◽  
S. Chevion ◽  
M. Chevion ◽  
M. Hofmann ◽  
P. Quehenberger ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Lipoic Acid ◽  
Alpha Lipoic Acid ◽  
Advanced Glycation ◽  
Advanced Glycation End Product ◽  
Cultured Endothelial Cells ◽  
Nf Kappab

The use of rosuvastatin and alpha lipoic acid in patients with unstable angina

2017 ◽  
Vol 23 (1-2) ◽  
pp. 9-14
Author(s):  
E.H. Zaremba ◽  
◽  
O.V. Smalyukh ◽  
O.V. Zaremba-Fedchyshyn ◽  
O.V. Zaremba ◽  
...  
Keyword(s):  
Unstable Angina ◽  
Lipoic Acid ◽  
Alpha Lipoic Acid
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