Ouabain increases iNOS-dependent nitric oxide generation which contributes to the hypertrophic effect of the glycoside: possible role of peroxynitrite formation

Gan, Xiaohong Tracey; Hunter, James C.; Huang, Cathy; Xue, Jenny Y.; Rajapurohitam, Venkatesh; Javadov, Sabzali; Karmazyn, Morris

doi:10.1007/s11010-011-1185-7

Cited by 6 publications

(3 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is consistent with observations in cardiac myocytes that ouabain increases ROS, an effect that was antagonized by a dominant negative Ras, suggesting Ras involvement in ROS generation [189]. Ouabain-induced nitrosative damage is also likely in cardiac myocytes, since iNOS, the form expressed in astrocytes is increased by ouabain [190].…”

Section: Cyclic Gmp and Nitric Oxidesupporting

confidence: 90%

Multifactorial Effects on Different Types of Brain Cells Contribute to Ammonia Toxicity

et al. 2016

View full text Add to dashboard Cite

Effects of ammonia on astrocytes play a major role in hepatic encephalopathy, acute liver failure and other diseases caused by increased arterial ammonia concentrations (e.g., inborn errors of metabolism, drug or mushroom poisoning). There is a direct correlation between arterial ammonia concentration, brain ammonia level and disease severity. However, the pathophysiology of hyperammonemic diseases is disputed. One long recognized factor is that increased brain ammonia triggers its own detoxification by glutamine formation from glutamate. This is an astrocytic process due to the selective expression of the glutamine synthetase in astrocytes. A possible deleterious effect of the resulting increase in glutamine concentration has repeatedly been discussed and is supported by improvement of some pathologic effects by GS inhibition. However, this procedure also inhibits a large part of astrocytic energy metabolism and may prevent astrocytes from responding to pathogenic factors. A decrease of the already low glutamate concentration in astrocytes due to increased synthesis of glutamine inhibits the malate-aspartate shuttle and energy metabolism. A more recently described pathogenic factor is the resemblance between NH and K in their effects on the Na,K-ATPase and the Na,K, 2 Cl and water transporter NKCC1. Stimulation of the Na,K-ATPase driven NKCC1 in both astrocytes and endothelial cells is essential for the development of brain edema. Na,K-ATPase stimulation also activates production of endogenous ouabains. This leads to oxidative and nitrosative damage and sensitizes NKCC1. Administration of ouabain antagonists may accordingly have therapeutic potential in hyperammonemic diseases.

show abstract

Section: Cyclic Gmp and Nitric Oxidesupporting

confidence: 90%

Multifactorial Effects on Different Types of Brain Cells Contribute to Ammonia Toxicity

et al. 2016

View full text Add to dashboard Cite

show abstract

“…These damages lead to many specific or general illnesses and problems, such as Keshan disease, stroke, neurotoxins, cancer, and renal graft glomerulonephritis [28]. Besides, ROS is accumulated with age [29], which is proposed to play roles in age-related illnesses, i.e. cancer and cardiovascular illness [30].…”

Section: Discussionmentioning

confidence: 99%

Ferulic Acid Orchestrates Anti-Oxidative Properties of Danggui Buxue Tang, an Ancient Herbal Decoction: Elucidation by Chemical Knock-Out Approach

et al. 2016

View full text Add to dashboard Cite

Ferulic acid, a phenolic acid derived mainly from a Chinese herb Angelica Sinensis Radix (ASR), was reported to reduce the formation of free radicals. Danggui Buxue Tang (DBT), a herbal decoction composing of Astragali Radix (AR) and ASR, has been utilized for more than 800 years in China having known anti-oxidative property. Ferulic acid is a major active ingredient in DBT; however, the role of ferulic acid within the herbal mixture has not been resolved. In order to elucidate the function of ferulic acid within this herbal decoction, a ferulic acid-depleted herbal decoction was created and named as DBTΔfa. The anti-oxidative properties of chemically modified DBT decoction were systemically compared in cultured H9C2 rat cardiomyoblast cell line. The application of DBT and DBTΔfa into the cultures showed functions in (i) decreasing the reactive oxygen species (ROS) formation, detected by laser confocal; (ii) increasing of the activation of Akt; (iii) increasing the transcriptional activity of anti-oxidant response element (ARE); and (iv) increasing the expressions of anti-oxidant enzymes, i.e. NQO1 and GCLM. In all scenario, the aforementioned anti-oxidative properties of DBTΔfa in H9C2 cells were significantly reduced, as compared to authentic DBT. Thus, ferulic acid could be an indispensable chemical in DBT to orchestrate multi-components of DBT as to achieve maximal anti-oxidative functions.

show abstract

“…The exclusiveness of this mechanism was challenged by the demonstration that the interaction of CS with Na 1 , K 1 -ATPase elicits the activation of several major signaling cascades, including ERK, Akt, and iNOS (Tian et al, 2001;Gan et al, 2012;Wu et al, 2013). The experiments were performed as described in the legend to Fig.…”

Section: Discussionmentioning

confidence: 99%

Essential Opposite Roles of ERK and Akt Signaling in Cardiac Steroid-Induced Increase in Heart Contractility

Buzaglo¹,

Rosen²,

Ami³

et al. 2016

The Journal of Pharmacology and Experimental Therapeutics

View full text Add to dashboard Cite

Interaction of cardiac steroids (CS) with the Na 1 , K 1 -ATPase elicits, in addition to inhibition of the enzyme's activity, the activation of intracellular signaling such as extracellular signalregulated (ERK) and protein kinase B (Akt). We hypothesized that the activities of these pathways are involved in CS-induced increase in heart contractility. This hypothesis was tested using in vivo and ex vivo wild type (WT) and sarcoplasmic reticulum Ca(21) atpase1a-deficient zebrafish (accordion, acc mutant) experimental model. Heart contractility was measured in vivo and in primary cardiomyocytes in WT zebrafish larvae and acc mutant. Ca 21 transients were determined ex vivo in adult zebrafish hearts. CS dose dependently augmented the force of contraction of larvae heart muscle and cardiomyocytes and increased Ca 21 transients in WT but not in acc mutant. CS in vivo increased the phosphorylation rate of ERK and Akt in the adult zebrafish heart of the two strains. Pretreatment of WT zebrafish larvae or cardiomyocytes with specific MAPK inhibitors completely abolished the CS-induced increase in contractility. On the contrary, pretreatment with Akt inhibitor significantly enhanced the CSinduced increase in heart contractility both in vivo and ex vivo without affecting CS-induced Ca 21 transients. Furthermore, pretreatment of the acc mutant larvae or cardiomyocytes with Akt inhibitor restored the CS-induced increase in heart contractility also without affecting Ca 21 transients. These results support the notion that the activity of MAPK pathway is obligatory for CS-induced increases in heart muscle contractility. Akt activity, on the other hand, plays a negative role, via Ca 21 independent mechanisms, in CS action. These findings point to novel potential pharmacological intervention to increase CS efficacy.

show abstract

Ouabain increases iNOS-dependent nitric oxide generation which contributes to the hypertrophic effect of the glycoside: possible role of peroxynitrite formation

Cited by 6 publications

References 40 publications

Multifactorial Effects on Different Types of Brain Cells Contribute to Ammonia Toxicity

Multifactorial Effects on Different Types of Brain Cells Contribute to Ammonia Toxicity

Ferulic Acid Orchestrates Anti-Oxidative Properties of Danggui Buxue Tang, an Ancient Herbal Decoction: Elucidation by Chemical Knock-Out Approach

Essential Opposite Roles of ERK and Akt Signaling in Cardiac Steroid-Induced Increase in Heart Contractility

Contact Info

Product

Resources

About