scholarly journals Akt Inhibition as Preconditioning Treatment to Protect Kidney Cells against Anoxia

2021 ◽  
Vol 23 (1) ◽  
pp. 152
Author(s):  
Nicolas Melis ◽  
Romain Carcy ◽  
Isabelle Rubera ◽  
Marc Cougnon ◽  
Christophe Duranton ◽  
...  
Keyword(s):  
Ischemia Reperfusion ◽  
Oxygen Demand ◽  
Ischemic Tolerance ◽  
Kidney Cells ◽  
Protective Mechanisms ◽  
Akt Phosphorylation ◽  
Mitochondrial Ros ◽  
Highly Sensitive ◽  
High Oxygen Demand ◽  
Survival Effect

Lesions issued from the ischemia/reperfusion (I/R) stress are a major challenge in human pathophysiology. Of human organs, the kidney is highly sensitive to I/R because of its high oxygen demand and poor regenerative capacity. Previous studies have shown that targeting the hypusination pathway of eIF5A through GC7 greatly improves ischemic tolerance and can be applied successfully to kidney transplants. The protection process correlates with a metabolic shift from oxidative phosphorylation to glycolysis. Because the protein kinase B Akt is involved in ischemic protective mechanisms and glucose metabolism, we looked for a link between the effects of GC7 and Akt in proximal kidney cells exposed to anoxia or the mitotoxic myxothiazol. We found that GC7 treatment resulted in impaired Akt phosphorylation at the Ser473 and Thr308 sites, so the effects of direct Akt inhibition as a preconditioning protocol on ischemic tolerance were investigated. We evidenced that Akt inhibitors provide huge protection for kidney cells against ischemia and myxothiazol. The pro-survival effect of Akt inhibitors, which is reversible, implied a decrease in mitochondrial ROS production but was not related to metabolic changes or an antioxidant defense increase. Therefore, the inhibition of Akt can be considered as a preconditioning treatment against ischemia.

scholarly journals The chromatin remodelling factor Chd7 protects auditory neurons and sensory hair cells from stress-induced degeneration

2021 ◽  
Author(s):  
Mohi Ahmed ◽  
Ruth Moon ◽  
Ravindra Singh Prajapati ◽  
Elysia James ◽  
M. Albert Basson ◽  
...  
Keyword(s):  
Hair Cells ◽  
Oxygen Demand ◽  
Cell Types ◽  
Charge Syndrome ◽  
Sensory Cells ◽  
Auditory Neurons ◽  
Protective Mechanisms ◽  
Multiple Organs ◽  
Sensory Hair Cells ◽  
High Oxygen Demand

Neurons and sensory cells are particularly vulnerable to oxidative stress due to their high oxygen demand during stimulus perception and transmission1-4. The mechanisms that protect them from stress-induced death and degeneration remain elusive. Here we show that embryonic deletion of the chromodomain helicase DNA-binding protein 7 (CHD7) in auditory neurons or hair cells leads to sensorineural hearing loss due to postnatal degeneration of both cell types. Mechanistically, we demonstrate that CHD7 controls the expression of major stress pathway components. In its absence, hair cells are hypersensitive, dying rapidly after brief exposure to stress inducers, suggesting that sound at the onset of hearing triggers their degeneration. In humans, CHD7 haploinsufficiency causes CHARGE syndrome, a disorder affecting multiple organs including the ear5,6. Our findings suggest that CHD7 mutations cause developmentally silent phenotypes that predispose cells to postnatal degeneration due to a failure of protective mechanisms.

scholarly journals Electroacupuncture Pretreatment as a Novel Avenue to Protect Brain against Ischemia and Reperfusion Injury

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Xin Li ◽  
Peng Luo ◽  
Qiang Wang ◽  
Lize Xiong
Keyword(s):  
High Risk ◽  
Reperfusion Injury ◽  
Recent Observation ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Tumor Resection ◽  
Ischemic Tolerance ◽  
Acute Ischemia ◽  
Preventive Strategy ◽  
Protective Mechanisms

Electroacupuncture (EA) pretreatment is a recent observation which has been shown to induce ischemic tolerance mimicking the ischemic pretreatment, suggesting that EA pretreatment may be a promising preventive strategy for the patients with high risk of acute ischemia/reperfusion injury. It was first described in the brain, then in the heart where EA stimulation at acupoint prior to ischemia led to neuroprotection and myocardial protection and induced rapid and delayed ischemic tolerance. Then the optimal parameters and acupoint specificity of EA pretreatment to induce protective effect were proved. Many studies have shown that protective mechanisms of EA pretreatment may involve a series of regulatory molecular pathways including activity enhancement of antioxidant, regulation of the endocannabinoid system, involvement ofbeta-adrenergic receptor, and postreceptor signaling pathway, inhibition of apoptosis. Recently, the neuroprotective and cardioprotective effect of EA pretreatment had been demonstrated in patients undergoing craniocerebral tumor resection or heart valve replacement surgery. Thus, the purpose of this paper is to collect the evidence for the neuroprotective effect of EA pretreatment, to summarize the proposed protective mechanisms of EA pretreatment, and to discuss the possibility of EA pretreatment as a new preventive strategy for patients with high risk of ischemia in clinic.

Activation of astroglial CB1R mediates cerebral ischemic tolerance induced by electroacupuncture

2021 ◽  
pp. 0271678X2199439
Author(s):  
Cen Yang ◽  
Jingjing Liu ◽  
Jingyi Wang ◽  
Anqi Yin ◽  
Zhenhua Jiang ◽  
...  
Keyword(s):  
Endocannabinoid System ◽  
Artery Occlusion ◽  
Ischemic Tolerance ◽  
Protective Mechanisms ◽  
Promising Therapeutic Approach ◽  
Subsequent Activation ◽  
Cerebral Ischemic ◽  
Cerebral Artery Occlusion ◽  
The Brain

There are no effective treatments for stroke. The activation of endogenous protective mechanisms is a promising therapeutic approach, which evokes the intrinsic ability of the brain to protect itself. Accumulated evidence strongly suggests that electroacupuncture (EA) pretreatment induces rapid tolerance to cerebral ischemia. With regard to mechanisms underlying ischemic tolerance induced by EA, many molecules and signaling pathways are involved, such as the endocannabinoid system, although the exact mechanisms have not been fully elucidated. In the current study, we employed mutant mice, neuropharmacology, microdialysis, and virus transfection techniques in a middle cerebral artery occlusion (MCAO) model to explore the cell-specific and brain region-specific mechanisms of EA-induced neuroprotection. EA pretreatment resulted in increased ambient endocannabinoid (eCB) levels and subsequent activation of ischemic penumbral astroglial cannabinoid type 1 receptors (CB1R) which led to moderate upregulation of extracellular glutamate that protected neurons from cerebral ischemic injury. These findings provide a novel cellular mechanism of EA and a potential therapeutic target for ischemic stroke.

scholarly journals Hepatic cell mobilization for protection against ischemic myocardial injury

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shu Q. Liu ◽  
John B. Troy ◽  
Chi-Hao Luan ◽  
Roger J. Guillory
Keyword(s):  
Ischemia Reperfusion ◽  
Hepatic Cell ◽  
Ischemic Myocardium ◽  
Cell Nuclei ◽  
Protective Mechanisms ◽  
Specific Expression ◽  
Time Points ◽  
Hepatic Cells ◽  
Cell Mobilization ◽  
Myocardial Ischemia Reperfusion

AbstractThe heart is capable of activating protective mechanisms in response to ischemic injury to support myocardial survival and performance. These mechanisms have been recognized primarily in the ischemic heart, involving paracrine signaling processes. Here, we report a distant cardioprotective mechanism involving hepatic cell mobilization to the ischemic myocardium in response to experimental myocardial ischemia–reperfusion (MI-R) injury. A parabiotic mouse model was generated by surgical skin-union of two mice and used to induce bilateral MI-R injury with unilateral hepatectomy, establishing concurrent gain- and loss-of-hepatic cell mobilization conditions. Hepatic cells, identified based on the cell-specific expression of enhanced YFP, were found in the ischemic myocardium of parabiotic mice with intact liver (0.2 ± 0.1%, 1.1 ± 0.3%, 2.7 ± 0.6, and 0.7 ± 0.4% at 1, 3, 5, and 10 days, respectively, in reference to the total cell nuclei), but not significantly in the ischemic myocardium of parabiotic mice with hepatectomy (0 ± 0%, 0.1 ± 0.1%, 0.3 ± 0.2%, and 0.08 ± 0.08% at the same time points). The mobilized hepatic cells were able to express and release trefoil factor 3 (TFF3), a protein mitigating MI-R injury as demonstrated in TFF3−/− mice (myocardium infarcts 17.6 ± 2.3%, 20.7 ± 2.6%, and 15.3 ± 3.8% at 1, 5, and 10 days, respectively) in reference to wildtype mice (11.7 ± 1.9%, 13.8 ± 2.3%, and 11.0 ± 1.8% at the same time points). These observations suggest that MI-R injury can induce hepatic cell mobilization to support myocardial survival by releasing TFF3.

scholarly journals Myocardial ischemic tolerance in rats subjected to endurance exercise training during adaptation to chronic hypoxia

2017 ◽  
Vol 122 (6) ◽  
pp. 1452-1461 ◽  
Author(s):  
Petra Alánová ◽  
Anna Chytilová ◽  
Jan Neckář ◽  
Jaroslav Hrdlička ◽  
Petra Míčová ◽  
...  
Keyword(s):  
Exercise Training ◽  
Infarct Size ◽  
Chronic Hypoxia ◽  
Ischemia Reperfusion ◽  
Ischemic Tolerance ◽  
Natural Stimuli ◽  
Size Limitation ◽  
Tnf Α ◽  
Protective Signaling

Chronic hypoxia and exercise are natural stimuli that confer sustainable cardioprotection against ischemia-reperfusion (I/R) injury, but it is unknown whether they can act in synergy to enhance ischemic resistance. Inflammatory response mediated by tumor necrosis factor-α (TNF-α) plays a role in the infarct size limitation by continuous normobaric hypoxia (CNH), whereas exercise is associated with anti-inflammatory effects. This study was conducted to determine if exercise training performed under conditions of CNH (12% O2) affects myocardial ischemic resistance with respect to inflammatory and redox status. Adult male Wistar rats were assigned to one of the following groups: normoxic sedentary, normoxic trained, hypoxic sedentary, and hypoxic trained. ELISA and Western blot analysis, respectively, were used to quantify myocardial cytokines and the expression of TNF-α receptors, nuclear factor-κB (NF-κB), and selected components of related signaling pathways. Infarct size and arrhythmias were assessed in open-chest rats subjected to I/R. CNH increased TNF-α and interleukin-6 levels and the expression of TNF-α type 2 receptor, NF-κB, inducible nitric oxide synthase (iNOS), cytosolic phospholipase A2α, cyclooxygenase-2, manganese superoxide dismutase (MnSOD), and catalase. None of these effects occurred in the normoxic trained group, whereas exercise in hypoxia abolished or significantly attenuated CNH-induced responses, except for NF-κB, iNOS, and MnSOD. Both CNH and exercise reduced infarct size, but their combination provided the same degree of protection as CNH alone. In conclusion, exercise training does not amplify the cardioprotection conferred by CNH. High ischemic tolerance of the CNH hearts persists after exercise, possibly by maintaining the increased antioxidant capacity despite attenuating TNF-α-dependent protective signaling. NEW & NOTEWORTHY Chronic hypoxia and regular exercise are natural stimuli that confer sustainable myocardial protection against acute ischemia-reperfusion injury. Signaling mediated by TNF-α via its type 2 receptor plays a role in the cardioprotective mechanism of chronic hypoxia. In the present study, we found that exercise training of rats during adaptation to hypoxia does not amplify the infarct size-limiting effect. Ischemia-resistant phenotype is maintained in the combined hypoxia-exercise setting despite exercise-induced attenuation of TNF-α-dependent protective signaling.

scholarly journals Diabetic Inhibition of Preconditioning- and Postconditioning-Mediated Myocardial Protection against Ischemia/Reperfusion Injury

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Xia Yin ◽  
Yang Zheng ◽  
Xujie Zhai ◽  
Xin Zhao ◽  
Lu Cai
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Protective Effect ◽  
Myocardial Protection ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Diabetic Patients ◽  
Protective Mechanisms ◽  
Gsk 3Β ◽  
Pathogenic Effects

Ischemic preconditioning (IPC) or postconditioning (Ipost) is proved to efficiently prevent ischemia/reperfusion injuries. Mortality of diabetic patients with acute myocardial infarction was found to be 2–6 folds higher than that of non-diabetic patients with same myocardial infarction, which may be in part due to diabetic inhibition of IPC- and Ipost-mediated protective mechanisms. Both IPC- and Ipost-mediated myocardial protection is predominantly mediated by stimulating PI3K/Akt and associated GSK-3β pathway while diabetes-mediated pathogenic effects are found to be mediated by inhibiting PI3K/Akt and associated GSK-3β pathway. Therefore, this review briefly introduced the general features of IPC- and Ipost-mediated myocardial protection and the general pathogenic effects of diabetes on the myocardium. We have collected experimental evidence that indicates the diabetic inhibition of IPC- and Ipost-mediated myocardial protection. Increasing evidence implies that diabetic inhibition of IPC- and Ipost-mediated myocardial protection may be mediated by inhibiting PI3K/Akt and associated GSK-3β pathway. Therefore any strategy to activate PI3K/Akt and associated GSK-3β pathway to release the diabetic inhibition of both IPC and Ipost-mediated myocardial protection may provide the protective effect against ischemia/reperfusion injuries.

Comparison of mayfly (Ephemeroptera) taxocenes of permanent and intermittent Central European small streams via species traits

Biologia ◽  
2010 ◽  
Vol 65 (4) ◽  
Author(s):  
Pavla Řezníčková ◽  
Tomáš Soldán ◽  
Petr Pařil ◽  
Světlana Zahrádková
Keyword(s):  
Global Climate ◽  
Extreme Temperature ◽  
Oxygen Demand ◽  
Hydrological Regime ◽  
Species Traits ◽  
Individual Species ◽  
Biological Traits ◽  
Small Streams ◽  
High Oxygen Demand ◽  
The Impact

AbstractThe recurrent drying out of small streams in past decades has shown an urgent need to pay attention to the impact of global climate change. The objectives of this study were to describe the effect of drying out on the composition of the mayfly taxocene and evaluate the relevance of individual species traits for survival of mayflies to drying out. The mayfly taxocenes of two model localities, one at an intermittent and one at a permanent brook, were investigated in 2002, 2003 and 2005. Compared with the permanent stream, the taxocene of the intermittent stream was short of nine species, foremost rheobionts and high oxygen demand species. To explain further differences between both stream types in survival and recolonisation ability, 15 species traits were evaluated. These included so-called “ecological traits” (e.g., habitat and substrate range, density, distribution, current velocity adaptation) and “biological traits” connected with life cycle and larval/adult adaptations. Species showing the highest number of advantageous traits (with only exception of Electrogena sp. cf. ujhelyii — species of taxonomically unclear status) were able to successfully survive under the unfavourable conditions of the intermittent brook. Biological traits considered more important in many respects seem to be good predictors for assessing sensitivity to extreme temperature changes, hydrological regime fluctuations and the survival/recolonisation ability of species in exposed habitats.

scholarly journals The Torpid State: Recent Advances in Metabolic Adaptations and Protective Mechanisms†

2021 ◽  
Vol 11 ◽  
Author(s):  
Sylvain Giroud ◽  
Caroline Habold ◽  
Roberto F. Nespolo ◽  
Carlos Mejías ◽  
Jérémy Terrien ◽  
...  
Keyword(s):  
Ischemia Reperfusion ◽  
Adaptive Strategy ◽  
Resistance Mechanisms ◽  
Tropical Species ◽  
Special Focus ◽  
Protective Mechanisms ◽  
Origin And Evolution ◽  
Metabolic Adaptations ◽  
Central Organ ◽  
Molecular Aspects

Torpor and hibernation are powerful strategies enabling animals to survive periods of low resource availability. The state of torpor results from an active and drastic reduction of an individual’s metabolic rate (MR) associated with a relatively pronounced decrease in body temperature. To date, several forms of torpor have been described in all three mammalian subclasses, i.e., monotremes, marsupials, and placentals, as well as in a few avian orders. This review highlights some of the characteristics, from the whole organism down to cellular and molecular aspects, associated with the torpor phenotype. The first part of this review focuses on the specific metabolic adaptations of torpor, as it is used by many species from temperate zones. This notably includes the endocrine changes involved in fat- and food-storing hibernating species, explaining biomedical implications of MR depression. We further compare adaptive mechanisms occurring in opportunistic vs. seasonal heterotherms, such as tropical and sub-tropical species. Such comparisons bring new insights into the metabolic origins of hibernation among tropical species, including resistance mechanisms to oxidative stress. The second section of this review emphasizes the mechanisms enabling heterotherms to protect their key organs against potential threats, such as reactive oxygen species, associated with the torpid state. We notably address the mechanisms of cellular rehabilitation and protection during torpor and hibernation, with an emphasis on the brain, a central organ requiring protection during torpor and recovery. Also, a special focus is given to the role of an ubiquitous and readily-diffusing molecule, hydrogen sulfide (H2S), in protecting against ischemia-reperfusion damage in various organs over the torpor-arousal cycle and during the torpid state. We conclude that (i) the flexibility of torpor use as an adaptive strategy enables different heterothermic species to substantially suppress their energy needs during periods of severely reduced food availability, (ii) the torpor phenotype implies marked metabolic adaptations from the whole organism down to cellular and molecular levels, and (iii) the torpid state is associated with highly efficient rehabilitation and protective mechanisms ensuring the continuity of proper bodily functions. Comparison of mechanisms in monotremes and marsupials is warranted for understanding the origin and evolution of mammalian torpor.

ERK promotes hydrogen peroxide-induced apoptosis through caspase-3 activation and inhibition of Akt in renal epithelial cells

2007 ◽  
Vol 292 (1) ◽  
pp. F440-F447 ◽  
Author(s):  
Shougang Zhuang ◽  
Yan Yan ◽  
Rebecca A. Daubert ◽  
Jiahuai Han ◽  
Rick G. Schnellmann
Keyword(s):  
Hydrogen Peroxide ◽  
Epithelial Cells ◽  
Caspase 3 ◽  
Ischemia Reperfusion ◽  
Nuclear Condensation ◽  
Histone H2b ◽  
Adenoviral Infection ◽  
Akt Phosphorylation ◽  
Renal Proximal Tubular Cells ◽  
Induced Apoptosis

Reactive oxygen species, including hydrogen peroxide (H2O2), are generated during ischemia-reperfusion and are critically involved in acute renal failure. The present studies examined the role of the extracellular signal-regulated kinase (ERK) pathway in H2O2-induced renal proximal tubular cells (RPTC) apoptosis. Exposure of RPTC to 1 mM H2O2resulted in apoptosis and activation of ERK1/2 and Akt. Pretreatment with the specific MEK inhibitors, U0126 and PD98059, or adenoviral infection with a construct that encodes a negative mutant of MEK1, protected cells against H2O2-induced apoptosis. In contrast, expression of constitutively active MEK1 enhanced H2O2-induced apoptosis. H2O2induced activation of caspase-3 and phosphorylation of histone H2B at serine 14, a posttranslational modification required for nuclear condensation, which also were blocked by ERK1/2 inhibition. Furthermore, blockade of ERK1/2 resulted in an increase in Akt phosphorylation and blockade of Akt potentiated apoptosis and diminished the protective effect conferred by ERK inhibition in H2O2-treated cells. Although Z-DEVD-FMK, a caspase-3 inhibitor, was able to inhibit histone H2B phosphorylation and apoptosis, it did not affect ERK1/2 phosphorylation. We suggest that ERK elicits apoptosis in epithelial cells by activating caspase-3 and inhibiting Akt pathways and elicits nuclear condensation through caspase-3 and histone H2B phosophorylation during oxidant injury.

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