α-Lipoic Acid Inhibits Endotoxin-stimulated Expression of iNOS and Nitric Oxide Independent of the Heat Shock Response in RAW 264.7 Cells

2004 ◽  
Vol 38 (7) ◽  
pp. 675-682 ◽  
Author(s):  
Vincent G. DeMarco ◽  
Philip O. Scumpia ◽  
James P. Bosanquet ◽  
Jeffrey W. Skimming
Keyword(s):  
Nitric Oxide ◽  
Heat Shock ◽  
Lipoic Acid ◽  
Heat Shock Response ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Shock Response

scholarly journals Alpha lipoic acid attenuates ER stress and improves glucose uptake through DNAJB3 cochaperone

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Abdoulaye Diane ◽  
Naela Mahmoud ◽  
Ilham Bensmail ◽  
Namat Khattab ◽  
Hanan A. Abunada ◽  
...  
Keyword(s):  
Heat Shock ◽  
Er Stress ◽  
Glucose Uptake ◽  
Lipoic Acid ◽  
Heat Shock Response ◽  
Transcriptional Activation ◽  
Hepg2 Cells ◽  
Metabolic Stress ◽  
C2c12 Cells ◽  
Shock Response

AbstractPersistent ER stress, mitochondrial dysfunction and failure of the heat shock response (HSR) are fundamental hallmarks of insulin resistance (IR); one of the early core metabolic aberrations that leads to type 2 diabetes (T2D). The antioxidant α-lipoic acid (ALA) has been shown to attenuate metabolic stress and improve insulin sensitivity in part through activation of the heat shock response (HSR). However, these studies have been focused on a subset of heat shock proteins (HSPs). In the current investigation, we assessed whether ALA has an effect on modulating the expression of DNAJB3/HSP40 cochaperone; a potential therapeutic target with a novel role in mitigating metabolic stress and promoting insulin signaling. Treatment of C2C12 cells with 0.3 mM of ALA triggers a significant increase in the expression of DNAJB3 mRNA and protein. A similar increase in DNAJB3 mRNA was also observed in HepG2 cells. We next investigated the significance of such activation on endoplasmic reticulum (ER) stress and glucose uptake. ALA pre-treatment significantly reduced the expression of ER stress markers namely, GRP78, XBP1, sXBP1 and ATF4 in response to tunicamycin. In functional assays, ALA treatment abrogated significantly the tunicamycin-mediated transcriptional activation of ATF6 while it enhanced the insulin-stimulated glucose uptake and Glut4 translocation. Silencing the expression of DNAJB3 but not HSP72 abolished the protective effect of ALA on tunicamycin-induced ER stress, suggesting thus that DNAJB3 is a key mediator of ALA-alleviated tunicamycin-induced ER stress. Furthermore, the effect of ALA on insulin-stimulated glucose uptake is significantly reduced in C2C12 and HepG2 cells transfected with DNAJB3 siRNA. In summary, our results are supportive of an essential role of DNAJB3 as a molecular target through which ALA alleviates ER stress and improves glucose uptake.

Cytokine-induced nitric oxide synthase gene transcription is blocked by the heat shock response in human liver cells

Surgery ◽  
1996 ◽  
Vol 120 (2) ◽  
pp. 144-149 ◽  
Author(s):  
Michael E. de Vera ◽  
James M. Wong ◽  
Jun-Ying Zhou ◽  
Edith Tzeng ◽  
Hector R. Wong ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Heat Shock ◽  
Nitric Oxide Synthase ◽  
Gene Transcription ◽  
Heat Shock Response ◽  
Human Liver ◽  
Liver Cells ◽  
Human Liver Cells ◽  
Shock Response ◽  
Oxide Synthase

The Heat Shock Response Inhibits NF-κB Activation, Nitric Oxide Synthase Type 2 Expression, and Macrophage/Microglial Activation in Brain

2000 ◽  
Vol 20 (5) ◽  
pp. 800-811 ◽  
Author(s):  
Michael T. Heneka ◽  
Anthony Sharp ◽  
Thomas Klockgether ◽  
Vitality Gavrilyuk ◽  
Douglas L. Feinstein
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Heat Shock ◽  
Nitric Oxide Synthase ◽  
Heat Shock Response ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Shock Response ◽  
Oxide Synthase

The heat shock response (HSR) provides protection against stress-induced damage, and also prevents initiation of inflammatory gene expression via inhibition of NFκB activation. This article describes experiments demonstrating that the HSR prevents induction of nitric oxide synthase type 2 (NOS2) in rat brain. Twenty four hours after intrastriatal injection of lipopolysaccharide (LPS), IL-1β, and IFN-γ, NOS2 immunoreactive cells were detected in striatum, corpus callosum, and to a lesser extent in cortex. Induction of a HSR by whole body warming to 41°C for 20 minutes, done 1 day before LPS plus cytokine injection, reduced the number of NOS2-positive staining cells to background levels. Staining for ED1 antigen revealed that the HSR also suppressed microglial/brain macrophage activation in the same areas. Striatal injection of LPS and cytokines induced the rapid activation of NFκB, and this activation was prevented by prior HS, which also increased brain IκB-α expression. These results suggest that establishment of a HSR can reduce inflammatory gene expression in brain, mediated by inhibition of NFκB activation, and may therefore offer a novel approach to treatment and prevention of neurological disease and trauma.

scholarly journals Differential hypoxic tolerance is mediated by activation of heat shock response and nitric oxide pathway

2014 ◽  
Vol 19 (6) ◽  
pp. 801-812 ◽  
Author(s):  
Kanika Jain ◽  
Geetha Suryakumar ◽  
Lilly Ganju ◽  
Shashi Bala Singh
Keyword(s):  
Nitric Oxide ◽  
Heat Shock ◽  
Heat Shock Response ◽  
Hypoxic Tolerance ◽  
Shock Response ◽  
Nitric Oxide Pathway

Heat shock response inhibits cytokine-inducible nitric oxide synthase expression in rat hepatocytes

Hepatology ◽  
1996 ◽  
Vol 24 (5) ◽  
pp. 1238-1245 ◽  
Author(s):  
M E de Vera ◽  
Y M Kim ◽  
H R Wong ◽  
Q Wang ◽  
T R Billiar ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Heat Shock ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Heat Shock Response ◽  
Rat Hepatocytes ◽  
Shock Response ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

scholarly journals L-Citrulline Influences the Body Temperature, Heat Shock Response and Nitric Oxide Regeneration of Broilers Under Thermoneutral and Heat Stress Condition

2021 ◽  
Vol 12 ◽  
Author(s):  
Victoria A. Uyanga ◽  
Minghui Wang ◽  
Tian Tong ◽  
Jingpeng Zhao ◽  
Xiaojuan Wang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Heat Stress ◽  
Heat Shock ◽  
Body Temperature ◽  
Mrna Expression ◽  
Heat Shock Response ◽  
Control Diet ◽  
The Body ◽  
No Production ◽  
Shock Response

Heat stress (HS) adversely affects several physiological responses in organisms, but the underlying molecular mechanisms involved are yet to be fully understood. L-Citrulline (L-Cit) is a nutraceutical amino acid that is gaining research interest for its role in body temperature regulation and nitric oxide synthesis. This study investigated whether dietary supplementation with L-Cit (1% of basal diet) could ameliorate the effects of acute HS on thermotolerance, redox balance, and inflammatory responses of broilers. Ross 308 broilers (288 chicks) were subjected to two environments; thermoneutral at 24°C (TNZ) or HS at 35°C for 5 h, and fed two diets; control or L-Cit. The results showed that HS increased the ear, rectal (RT), and core body (CBT) temperatures of broilers, along with higher respiratory rate. The RT and CBT readings were intermittently affected with time effect, whereas, L-Cit supplementation lowered the mean CBT than the control diet. Antioxidant assays showed that superoxide dismutase was increased during HS, while, catalase was promoted by L-Cit supplementation. In addition, L-Cit induced glutathione peroxidase activity compared to the control diet during HS. Hypothalamic heat shock protein (HSP)-90 was upregulated by HS, but L-Cit downregulated heat shock factor (HSF)-1, and HSP 60 mRNA expressions. HSF 3 mRNA expression was downregulated by L-Cit under TNZ condition. More so, HS increased the plasma nitric oxide (NO) concentration but lowered the total NO synthase (tNOS) activity. In contrast, L-Cit supplementation limited NO production but increased the tNOS activity. Arginase activity was increased in the control fed group during HS but L-Cit supplementation lowered this effect. The NOS-COX pathway was significantly affected under TNZ condition, since L-Cit supplementation downregulated the mRNA expression of iNOS-COX2 in the hypothalamus, and further reduced the serum PGE2 concentration. Together, these data indicates that L-Cit influenced the antioxidant defense, heat shock response and nitric oxide regeneration both under thermoneutral and HS conditions; and that L-Cit may be directly and/or indirectly involved in the central regulation of body temperature.

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