Role of calcium in adaptive cytoprotection and cell injury induced by deoxycholate in human gastric cells

1998 ◽  
Vol 275 (2) ◽  
pp. G322-G330 ◽  
Author(s):  
Evan R. Kokoska ◽  
Gregory S. Smith ◽  
Andrew B. Wolff ◽  
Yashwant Deshpande ◽  
Christopher L. Rieckenberg ◽  
...  
Keyword(s):  
Cellular Response ◽  
Cell Injury ◽  
Protective Action ◽  
Cellular Injury ◽  
Adaptive Cytoprotection ◽  
Gastric Cells ◽  
Intracellular Ca ◽  
High Concentrations ◽  
Mild Irritant

We have developed an in vitro model of adaptive cytoprotection induced by deoxycholate (DC) in human gastric cells and have shown that pretreatment with a low concentration of DC (mild irritant, 50 μM) significantly attenuates injury induced by a damaging concentration of DC (250 μM). This study was undertaken to assess the effect of the mild irritant on changes in intracellular Ca2+ and to determine if these perturbations account for its protective action. Protection conferred by the mild irritant was lost when any of its effects on intracellular Ca2+ were prevented: internal Ca2+ store release via phospholipase C and inositol 1,4,5-trisphosphate sustained Ca2+ influx through store-operated Ca2+ channels or eventual Ca2+ efflux. We also investigated the relationship between Ca2+accumulation and cellular injury induced by damaging concentrations of DC. In cells exposed to high concentrations of DC, sustained Ca2+ accumulation as a result of extracellular Ca2+ influx, but not transient changes in intracellular Ca2+ content, appeared to precede and induce cellular injury. We propose that the mild irritant disrupts normal Ca2+ homeostasis and that this perturbation elicits a cellular response (involving active Ca2+ efflux) that subsequently provides a protective action by limiting the magnitude of intracellular Ca2+ accumulation.

Freeze-thaw injury in erythrocytes of the freeze-tolerant wood frog, Rana sylvatica

1991 ◽  
Vol 261 (6) ◽  
pp. R1346-R1350 ◽  
Author(s):  
J. P. Costanzo ◽  
R. E. Lee
Keyword(s):  
Cell Injury ◽  
Osmotic Fragility ◽  
Rana Sylvatica ◽  
Freeze Tolerance ◽  
Wood Frog ◽  
In Vitro Tests ◽  
Freezing And Thawing ◽  
Freeze Tolerant ◽  
High Concentrations

Erythrocytes from the freeze-tolerant wood frog (Rana sylvatica) were subjected to in vitro tests of freeze tolerance, cryoprotection, and osmotic fragility. The responses of cells from frogs acclimated to 4 or 15 degrees C were similar. Erythrocytes that were frozen in saline hemolyzed at -4 degrees C or lower. The addition of high concentrations (150 and 1,500 mM) of glucose or glycerol, cryoprotectants produced naturally by freeze-tolerant frogs, significantly reduced cell injury at -8 degrees C, but concentrations of 1.5 or 15 mM were ineffective. Hemolysis was reduced by 94% with 1,500 mM glycerol and by 84% with 1,500 mM glucose; thus glycerol was the more effective cryoprotectant. Mean fragility values for frog erythrocytes incubated in hypertonic and hypotonic saline were 1,938 and 49 mosM, respectively. Survival in freeze tolerance and cryoprotection experiments was comparable for erythrocytes from frogs and humans, suggesting that these cells may respond similarly to freezing-related stresses. However, the breadth of osmotic tolerance, standardized for differences in isotonicity, was greater for frog erythrocytes than for human erythrocytes. Our data suggest that erythrocytes from R. sylvatica are adequately protected by glucose under natural conditions of freezing and thawing.

Adaptive cytoprotection in the small intestine: role of mucus

1993 ◽  
Vol 264 (5) ◽  
pp. G921-G927 ◽  
Author(s):  
G. Cepinskas ◽  
R. D. Specian ◽  
P. R. Kvietys
Keyword(s):  
Small Intestine ◽  
Oleic Acid ◽  
Epithelial Cell ◽  
Cell Injury ◽  
Sodium Taurocholate ◽  
Dependent Manner ◽  
Adaptive Cytoprotection ◽  
Epithelial Integrity ◽  
Epithelial Cell Injury

Gastric mucosal injury induced by strong irritants can be dramatically reduced by pretreating the mucosa with mild forms of the same irritant. This phenomenon has been termed "adaptive cytoprotection." The aim of the present study was to use in vivo and in vitro approaches to study adaptive cytoprotection in the small intestine using physiologically relevant concentrations of oleic acid. Anesthetized rats were instrumented for perfusion of the proximal jejunum with 10 or 40 mM oleic acid (in 20 mM sodium taurocholate). Mucosal epithelial integrity was continuously monitored by measuring the blood-to-lumen clearance of 51Cr-labeled EDTA. Perfusion of the lumen with 40 mM oleic acid produced a 10-fold increase in 51Cr-EDTA clearance, which was not affected by a previous perfusion with 10 mM oleic acid, i.e., no adaptive cytoprotection. In another series of experiments, oleic acid was placed in the lumen rather than perfused, and mucosal epithelial integrity was assessed histologically. Intraluminal placement of 10 mM oleic acid resulted in the generation of a mucus layer over the epithelium. Subsequent placement of 40 mM oleic acid did not produce significant epithelial cell injury, i.e., adaptive cytoprotection. In in vitro studies, mucin (1, 5, and 10 mg/ml) was layered over confluent monolayers of Caco-2 cells prior to addition of 2 mM oleic acid in 4 mM sodium taurocholate. The epithelial cell injury induced by oleic acid was inhibited by mucin in a dose-dependent manner. Further studies indicate that mucin does not prevent, but simply delays, the onset of cell injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of extracellular acidosis on 45Ca uptake in isolated hypoxic proximal tubules

1988 ◽  
Vol 254 (6) ◽  
pp. C839-C846 ◽  
Author(s):  
M. Burnier ◽  
V. J. Van Putten ◽  
A. Schieppati ◽  
R. W. Schrier
Keyword(s):  
Cell Injury ◽  
Morphological Changes ◽  
Proximal Tubules ◽  
Cellular Damage ◽  
Hypoxic Cell ◽  
Cellular Injury ◽  
45Ca Uptake ◽  
Extracellular Acidosis ◽  
Cellular Ca

Recent in vitro studies have suggested that the presence of extracellular acidosis is protective against the development of oxygen-deprivation injury in several tissues. Because cellular Ca accumulation after renal ischemia may represent a major pathogenic event leading to cellular damage, the purpose of the present study was to examine the effect of extracellular acidosis on 45Ca uptake and desaturation in normal and hypoxic isolated rat proximal tubules. At pH 7.4, an increase in 45Ca uptake was observed in proximal tubules after 30 min of hypoxia. In addition, 45Ca desaturation was increased significantly in hypoxic tubules at pH 7.4. The alterations in 45Ca uptake and desaturation in hypoxic tubules at pH 7.4 were accompanied by significant signs of cellular injury as assessed by the amount of lactate dehydrogenase (LDH) released by the tubules at the end of the hypoxic period (22.5% above control tubules, P less than 0.01) as well as in morphological changes consistent with hypoxic cell injury. In contrast, when maintained at pH 6.9 throughout the study, no difference in 45Ca uptake or desaturation was observed between the control and hypoxic tubules; the hypoxic proximal tubules exhibited a smaller increase in LDH release (12.7% above control tubules) and did not develop the morphological changes observed at pH 7.4. Thus, during hypoxia and reoxygenation at pH 7.4, the increased 45Ca uptake may contribute in part to cellular injury in rat proximal tubules.

scholarly journals Calcium mediated functional interplay between myocardial cells upon laser-induced single-cell injury: an in vitro study of cardiac cell death signaling mechanisms

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Krishna Chander Sridhar ◽  
Nils Hersch ◽  
Georg Dreissen ◽  
Rudolf Merkel ◽  
Bernd Hoffmann
Keyword(s):  
Cell Death ◽  
Single Cell ◽  
Cell Injury ◽  
Specific Effect ◽  
Myocardial Cell ◽  
Myocardial Tissue ◽  
Cell Clusters ◽  
Signaling Events ◽  
Intracellular Ca

Abstract Background The electromechanical function of myocardial tissue depends on the intercellular communication between cardiomyocytes (CMs) as well as their crosstalk with other cell types. Cell injury, and subsequent death trigger inflammation as in myocardial infarction (MI) resulting in myocardial remodeling. Although mechanisms underlying myocardial cell death have been studied so far, the signaling events following single cell death and spontaneous response of connected cells in the myocardial tissue is still barely understood. Methods Here, we investigated the effect of laser-induced single cell death on Calcium (Ca2+) concentrations and transport in myocardial cell clusters in vitro. Spatial and temporal changes in intracellular Ca2+ concentrations [Ca2+]i were studied using a fluorescent calcium indicator, Fluo-4AM. Spontaneous signaling events following cell death were studied in rat embryonic cardiomyocytes and non-myocytes using separate cell culture systems. Results Cell death triggered spontaneous increase in intracellular Ca2+ levels ([Ca2+]i) of surrounding cells. The spread of the observed propagating Ca2+ signal was slow and sustained in myocytes while it was rapid and transient in fibroblasts (Fbs). Further, sustained high Ca2+ levels temporarily impaired the contractility in CMs. The cell-type specific effect of ablation was confirmed using separate cultures of CMs and Fbs. Comparing Ca2+ propagation speed in myocytes and fibroblasts, we argue for a diffusion-driven Ca2+ propagation in myocytes, but not in fibroblasts. Radial and sequential Ca2+ diffusion across the CMs through cell–cell contacts and presence of Cx43-based intercellular junctions indicated a gap junction flow of Ca2+. Conclusions These findings illustrate the spontaneous Ca2+-mediated functional interplay in myocardial cell clusters upon mechanical injury and, further, the difference in Ca2+ signaling in cardiomyocytes and fibroblasts.

scholarly journals Ionophore Ability of Carnosine and Its Trehalose Conjugate Assists Copper Signal in Triggering Brain-Derived Neurotrophic Factor and Vascular Endothelial Growth Factor Activation In Vitro

2021 ◽  
Vol 22 (24) ◽  
pp. 13504
Author(s):  
Irina Naletova ◽  
Valentina Greco ◽  
Sebastiano Sciuto ◽  
Francesco Attanasio ◽  
Enrico Rizzarelli
Keyword(s):  
Tyrosine Kinase ◽  
Protective Action ◽  
Protective Role ◽  
Copper Binding ◽  
Molecular Features ◽  
Mammalian Tissues ◽  
Kinase Cascade ◽  
High Concentrations ◽  
Endothelial Growth Factor

l-carnosine (β-alanyl-l-histidine) (Car hereafter) is a natural dipeptide widely distributed in mammalian tissues and reaching high concentrations (0.7–2.0 mM) in the brain. The molecular features of the dipeptide underlie the antioxidant, anti-aggregating and metal chelating ability showed in a large number of physiological effects, while the biological mechanisms involved in the protective role found against several diseases cannot be explained on the basis of the above-mentioned properties alone, requiring further research efforts. It has been reported that l-carnosine increases the secretion and expression of various neurotrophic factors and affects copper homeostasis in nervous cells inducing Cu cellular uptake in keeping with the key metal-sensing system. Having in mind this l-carnosine ability, here we report the copper-binding and ionophore ability of l-carnosine to activate tyrosine kinase cascade pathways in PC12 cells and stimulate the expression of BDNF. Furthermore, the study was extended to verify the ability of the dipeptide to favor copper signaling inducing the expression of VEGF. Being aware that the potential protective action of l-carnosine is drastically hampered by its hydrolysis, we also report on the behavior of a conjugate of l-carnosine with trehalose that blocks the carnosinase degradative activity. Overall, our findings describe a copper tuning effect on the ability of l-carnosine and, particularly its conjugate, to activate tyrosine kinase cascade pathways.

scholarly journals Effect of Nardostachys jatamansi DC. on Apoptosis, Inflammation and Oxidative Stress Induced by Doxorubicin in Wistar Rats

Plants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1579
Author(s):  
Mhaveer Singh ◽  
Mohammad Ahmed Khan ◽  
Kamal Y. T. ◽  
Javed Ahmad ◽  
Usama A. Fahmy ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Injury ◽  
Protective Action ◽  
Total Phenolic ◽  
High Dose ◽  
Cardiac Tissues ◽  
Nardostachys Jatamansi ◽  
Histopathological Evaluation

The study aimed to investigate the protective action of jatamansi (Nardostachys jatamansi DC.) against doxorubicin cardiotoxicity. Methanolic extract of jatamansi (MEJ) was prepared and standardized using HPTLC fingerprinting, GC-MS chemoprofiling, total phenolic content, and antioxidant activity in vitro. Further in vivo activity was evaluated using rodent model. Animals were divided into five groups (n = 6) namely control (CNT) (Normal saline), toxicant (TOX, without any treatment), MEJ at low dose (JAT1), MEJ at high dose (JAT2), and standard desferrioxamine (STD). All groups except control received doxorubicin 2.5 mg per Kg intra-peritoneally for 3 weeks in twice a week regimen. After 3 weeks, the blood samples and cardiac tissues were collected from all groups for biochemical and histopathological evaluation. Treatment with MEJ at both dose levels exhibited significant reduction (p < 0.001 vs. toxicant) of serum CK-MB (heart creatine kinase), LDH (Lactate dehydrogenase) & HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) levels, and tissue MDA (melondialdehyde) level; insignificant difference was observed (p > 0.05) in TNF-alpha (tumour necrosis factor), IL-6 (interleukine-6) levels and caspase activity as compared to TOX. Histopathological evaluation of cardiac tissues of different treatment groups further reinforced the findings of biochemical estimation. This study concludes that jatamansi can protect cardiac tissues from oxidative stress-induced cell injury and lipid peroxidation as well as against inflammatory and apoptotic effects on cardiac tissues.

Protective action of gastrin-17 against alcohol-induced gastric injury in the rat: role in mucosal defense

1997 ◽  
Vol 273 (2) ◽  
pp. G365-G373 ◽  
Author(s):  
D. W. Mercer ◽  
J. M. Cross ◽  
G. S. Smith ◽  
T. A. Miller
Keyword(s):  
Receptor Antagonist ◽  
Protective Action ◽  
Mucosal Blood Flow ◽  
Gastric Mucosal Blood Flow ◽  
Gastric Injury ◽  
Protective Effects ◽  
Adaptive Cytoprotection ◽  
Gastrin Receptor ◽  
Mucosal Defense ◽  
Mild Irritant

Exogenous cholecystokinin (CCK) or exposure of the stomach to the mild irritant 25% ethanol can prevent gastric injury. Ingestion of ethanol also elicits the release of CCK as well as gastrin, which is structurally similar to CCK. This study was undertaken in conscious rats to examine the gastroprotective actions of gastrin and to assess the effect of CCK-gastrin receptor blockade on adaptive cytoprotection with ethanol as the mild irritant. Intravenous (1-25 pmol/kg) administration of gastrin-17 dose dependently increased gastric mucosal blood flow (laser Doppler) and reduced gastric injury caused by 1 ml of orally administered acidified ethanol (150 mM HCl-50% ethanol). Similar gastroprotection was achieved with the gastrin secretagogue 5% peptone (1 ml orogastrically). The gastroprotective capabilities of gastrin-17 were attenuated by the type B CCK (gastrin) receptor antagonist L-365,260 (12.5-25 mg/kg i.p.) and by capsaicin desensitization (125 mg/kg s.c.). CCK octapeptide (5 nmol/kg i.v.)-induced protection was reversed by the type A CCK receptor antagonist MK-329 (1 mg/kg i.p.). Neither receptor antagonist, alone or in combination, reversed the protective effects of the mild irritant 25% ethanol (1 ml orogastrically). Thus, whereas gastrin may play a role in gastric mucosal defense, neither CCK nor gastrin appears to participate in the phenomenon of adaptive cytoprotection.

scholarly journals lncRNA SNHG14 Plays a Role in Sepsis-Induced Acute Kidney Injury by Regulating miR-93

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Chuanchuan Shi ◽  
Yuqian Zhao ◽  
Qi Li ◽  
Jianguo Li
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Noncoding Rna ◽  
Poor Prognosis ◽  
Cell Injury ◽  
Kidney Injury ◽  
Organ Injury ◽  
Cellular Injury ◽  
Stat3 Signaling

Acute kidney injury (AKI) is a common organ injury in sepsis, which leads to poor prognosis. Long noncoding RNA (lncRNA) small nucleolus RNA host gene 14 (SNHG14) was recognized to induce cell injury in LPS-induced acute lung injury and Parkinson’s disease. We want to investigate the functions and mechanisms of SNHG14 in sepsis-induced AKI. Increased expression of SNHG14 was observed in LPS-induced HK-2 cells, and this was due to the activation of the TLR4/NF-κB pathway. In vitro studies showed that SNHG14 was involved in the oxidative stress, inflammation, and apoptosis of LPS-induced HK-2 cells. Further investigations confirmed that SNHG14 exerted the functions via miR-93 which could regulate the activation of NF-κB and STAT3 signaling by targeting IRAK4 and IL-6R. We also found that silencing SNHG14 also alleviated cellular injury processes of IL-1β and IL-6 in HK-2 cells via miR-93. We demonstrate that SNHG14 accelerates cellular injury in sepsis-induced AKI by activating IRAK4/NF-κB and IL-6R/STAT3 signaling via miR-93.

Injury Of Cultured Endothelial Cells By Thrombin-Stimulated Platelets

1981 ◽  
Author(s):  
L Jørgensen ◽  
A G Grøthe ◽  
T Larsen ◽  
R L Kinlough-Rathbone ◽  
J F Mustard
Keyword(s):  
Endothelial Cells ◽  
Cell Injury ◽  
Intercellular Junctions ◽  
Ambient Fluid ◽  
Culture Dish ◽  
Platelet Suspension ◽  
Significant Release ◽  
High Concentrations

Platelets stimulated in vivo may cause endothelial injury. The question is whether a similar effect of platelet stimulation may be shown in vitro.Endothelial cells were cultured from human umbilical veins in Medium 199 with 20 per cent heat-inactivated serum. Semiconfluent cultures, 100-400.000 cells per dish, were labelled with Na2Cr51O4. Twenty-four hours later human platelet suspension (final cone. 200.000 per mm3) and thrombin (final cone. 4 U/ml) were added to the medium and the culture dish shaken for 15 min. The percentage of cells detached from the culture dish and the percentage of Cr51 released from the endothelial cells into the ambient fluid during the shaking were determined and used as parameters of cell injury. Increased percentages of loosened cells and Cr51 into the ambient fluid were observed with platelet suspension and thrombin compared to controls without platelet suspension and/or thrombin. Platelet-free supernatant after reaction of thrombin with platelet suspension had a similar effect. Thrombin alone caused a moderat release of Cr51, but no increased loosening of cells. Both parameters increased with increasing dose of thrombin when the platelet count was kept constant. The percentage of loosened cells increased with increasing platelet number when the dose of thrombin was constant. A significant release of Cr51 occurred only at high concentrations of platelets. Scanning and transmission electron microscopy of endothelial cells exposed to thrombin-stimulated platelets confirmed the presence of loosening and injured cells in association with platelets. The endothelial cells were bulging, intercellular junctions opened up, the plasma membrane on the luminal side showed villi and breaks and the cytoplasm had increased electron density. Thus, platelets stimulated by thrombin may cause injury of endothelial cells also in vitro.

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