Peptides GWN and GW protect kidney cells against Dasatinib induced mitochondrial injury in a SIRT1 dependent manner

Cordyceps militaris (L.) Link is an entomopathogenic fungus parasitic to Lepidoptera larvae, and is widely used as a folk tonic or invigorant for longevity in China. Although C. militaris has been used in traditional Chinese medicine for millennia, there is still a lack convincing evidence for its anti-aging activities. This study was performed to investigate the effects of polysaccharides from cultivated fruiting bodies of C. militaris (CMP) on mitochondrial injury, antioxidation and anti-aging activity. Fruiting bodies of C. militaris were cultivated artificially under optimized conditions. The spectrophotometric method was used to measure thiobarbituric acid reactive substances (TBARS), mitochondrial swelling, and activities of scavenging superoxide anions in vitro. D-galactose (100 mg/kg/day) was injected subcutaneously into back of the neck of mice for 7 weeks to induce an aging model. The effects of CMP on the activities of catalase (CAT), surperoxide dismutase (SOD), glutathione peroxidase (GPx) and anti-hydroxyl radicals were assayed in vivo using commercial monitoring kits. The results showed that CMP could inhibit mitochondrial injury and swelling induced by Fe2+ -L-Cysteine in a concentration- dependent manner and it also had a significant superoxide anion scavenging effect. Moreover, the activities of CAT, SOD, GPx and anti-hydroxyl radicals in mice liver were increased significantly by CMP. These results indicate that CMP protects mitochondria by scavenging reactive oxygen species (ROS), inhibiting mitochondrial swelling, and increasing the activities of antioxidases. Therefore, CMP may have pharmaceutical values for mitochondrial protection and anti-aging. CMP was the major bioactive component in C. militaris.

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Molecular mechanisms underlying the sensing of extracellular Ca2+ by parathyroid and kidney cells

Acta Endocrinologica ◽

10.1530/eje.0.1320523 ◽

1995 ◽

Vol 132 (5) ◽

pp. 523-531 ◽

Cited By ~ 12

Author(s):

Edward M Brown ◽

Martin Pollak ◽

Steven C Hebert

Keyword(s):

G Protein ◽

Molecular Mechanisms ◽

Ion Homeostasis ◽

Indirect Evidence ◽

Second Messenger ◽

Cell Surface Receptor ◽

Expression Cloning ◽

Kidney Cells ◽

Dependent Manner ◽

Inherited Disorders

Brown EM, Pollak M, Hebert SC. Molecular mechanisms underlying the sensing of extracellular Ca2+ by parathyroid and kidney cells. Eur J Endocrinol 1995;132:523–31. ISSN 0804–4643 Mineral ion homeostasis in mammalian species is maintained by a complex mechanism comprising sensors of the extracellular calcium concentration (Ca02+) (i.e. parathyroid cells) as well as effectors that modify their translocation of mineral ions into and out of the extracellular fluid (e.g. kidney) in response to calciotropic hormones. Indirect evidence accumulated over the past decade suggested that parathyroid cells sense Ca02+ through a cell surface receptor coupled to intracellular second messenger systems via one or more guanine nucleotide regulatory (G) proteins. More recently, Brown et al. employed expression cloning in Xenopus laevis oocytes to isolate a cDNA encoding a Ca02+-sensing receptor from bovine parathyroid. The expressed receptor activates phospholipase C in a G-protein dependent manner and shows pharmacological properties almost identical to those of the native parathyroid receptor. Agonists for the receptor include not only divalent cations (e.g. Ca2+ and Mg2+) but also trivalent cations and even organic polycations such as neomycin. The deduced amino acid sequence of the cloned receptor confirms that it is a member of the superfamily of G-protein-coupled receptors. Receptor transcripts are present in parathyroid as well as in kidney, thyroid and brain. Therefore, this receptor may mediate the sensing of Ca02+ not only by parathyroid cells but also by other tissues directly regulated by Ca02+ (e.g. the thyroidal C cells and certain kidney cells) as well as those not currently known to be involved in calcium homeostasis (viz. in the brain). Further evidence for the physiological relevance of the receptor comes from the discovery that mutations in the human homolog of the Ca02+-sensing receptor gene cause three inherited disorders of mineral ion homeostasis. Familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism are the clinical expression of inactivating mutations of the receptor when present in the heterozygous and homozygous state, respectively. An autosomal dominant form of hypocalcemia, on the other hand, results from an activating mutation of the receptor. Thus, this Ca02+-sensing receptor permits Ca02+ to act, in effect, as an extracellular first messenger in addition to its more widely recognized role as an intracellular second messenger. Edward M Brown, Endocrine–Hypertension Division, Brigham and Women's Hospital, 221 Longwood Ave, Boston, MA02115, USA

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Congener-Specific Polychlorinated Biphenyl–Induced Cell Death in Human Kidney Cells In Vitro: Potential Role of Caspase

International Journal of Toxicology ◽

10.1080/10915810600840859 ◽

2006 ◽

Vol 25 (5) ◽

pp. 341-347 ◽

Cited By ~ 12

Author(s):

Y. Q. Chen ◽

S. De ◽

S. Ghosh ◽

S. K. Dutta

Keyword(s):

Cell Death ◽

Proximal Tubule ◽

Human Kidney ◽

Renal Proximal Tubule ◽

Proximal Tubule Cell ◽

Kidney Cells ◽

Dependent Manner ◽

Caspase Inhibitor ◽

Pcb Congeners

Polychlorinated biphenyls (PCBs) are among the most widespread and persistent pollutants in the global environment. Coplanar and noncoplanar PCBs have been shown to cause congener-specific apoptosis mediated neurotoxicity in rats. Very few, if any, such studies have been reported on human renal cell toxicity. The authors report here caspase-dependent or caspase-independent renal toxicity, as measured by apoptotic death induced by PCBs, depending on the planarity of congeners PCB-77 (coplanar) and PCB-153 (noncoplanar) in human kidney cells (HK2) in vitro. The authors have combined morphological and biological techniques to discover the relevance of apoptosis in renal proximal tubule cell death induced by these two PCB congeners. Treatment with both PCB congeners caused accelerated apoptosis in a time-and concentration-dependent manner. Based on our findings using human kidney (HK2) cells, there was more apoptosis-mediated loss of cell viability by non– ortho-substituted PCB-77 when compared to PCB-153. A significant increase of caspase-3 expression through immunoblot studies showed the involvement of apoptosis by PCB-77 compared to none by PCB-153. The broad-spectrum caspase inhibitor z-VAD-fmk showed increased cell death when treated by PCB-153, but not by PCB-77, confirming that caspase inhibitor induced a switch in the mode of cell death. It is reasonable to assume that apoptotic cell death in the renal proximal tubule cells treated by PCBs may have both caspase-dependent and caspase-independent pathways.

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Ketamine Inhibits Monoamine Transporters Expressed in Human Embryonic Kidney 293 Cells

Anesthesiology ◽

10.1097/00000542-199803000-00029 ◽

1998 ◽

Vol 88 (3) ◽

pp. 768-774 ◽

Cited By ~ 76

Author(s):

Mitsuhiro Nishimura ◽

Kohji Sato ◽

Tomoya Okada ◽

Ikuto Yoshiya ◽

Patrick Schloss ◽

...

Keyword(s):

Eukaryotic Expression ◽

Psychotic Symptoms ◽

Kidney Cells ◽

Dependent Manner ◽

Monoamine Transporters ◽

Human Embryonic Kidney ◽

General Anesthetic ◽

Serotonin Transporters ◽

Human Embryonic Kidney Cells ◽

Dose Dependent

Background Ketamine has been characterized as having psychotomimetic and sympathomimetic effects. These symptoms have raised the possibility that ketamine affects monoaminergic neurotransmission. To elucidate the relation between ketamine and monoamine transporters, the authors constructed three cell lines that stably express the norepinephrine, dopamine, and serotonin transporters and investigated the effects of ketamine on these transporters. Methods Human embryonic kidney cells were transfected using the Chen-Okayama method with the human norepinephrine, rat dopamine, and rat serotonin transporter cDNA subcloned into the eukaryotic expression vector. Using cells stably expressing these transporters, the authors investigated the effects of ketamine on the uptake of these compounds and compared them with those of pentobarbital. Results Inhibition analysis showed that ketamine significantly inhibited the uptake of all three monoamine transporters in a dose-dependent manner. The Ki (inhibition constant) values of ketamine on the norepinephrine, dopamine, and serotonin transporters were 66.8 microM, 62.9 microM, and 162 microM, respectively. Pentobarbital, a typical general anesthetic agent with no psychotic symptoms, did not affect the uptake of monoamines, however. Further, neither the glycine transporter 1 nor the glutamate/aspartate transporter was affected by ketamine, indicating that ketamine preferentially inhibits monoamine transporters. Conclusions Ketamine inhibited monoamine transporters expressed in human embryonic kidney cells in a dose-dependent manner. This result suggests that the ketamine-induced inhibition of monoamine transporters might contribute to its psychotomimetic and sympathomimetic effects through potentiating monoaminergic neurotransmission.

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Effects of compound probiotics and aflatoxin-degradation enzyme on alleviating aflatoxin-induced cytotoxicity in chicken embryo primary intestinal epithelium, liver and kidney cells

10.21203/rs.3.rs-127834/v2 ◽

2021 ◽

Author(s):

Hongwei Guo ◽

Juan Chang ◽

Ping Wang ◽

Qingqiang Yin ◽

Chaoqi Liu ◽

...

Keyword(s):

Intestinal Epithelium ◽

Kidney Cell ◽

Chicken Embryo ◽

Cell Damage ◽

Kidney Cells ◽

Dependent Manner ◽

Damage Models ◽

Liver And Kidney ◽

Aflatoxin B ◽

Epithelium Cells

Abstract Aflatoxin B1 (AFB1) is one of the most dangerous mycotoxins for humans and animals. This study aimed to investigate the effects of compound probiotics (CP), CP supernatant (CPS), AFB1-degradation enzyme (ADE) on chicken embryo primary intestinal epithelium, liver and kidney cell viabilities, and to determine the functions of CP + ADE (CPADE) or CPS + ADE (CPSADE) for alleviating cytotoxicity induced by AFB1. The results showed that AFB1 decreased cell viabilities in dose-dependent and time-dependent manner. The optimal AFB1 concentrations and reactive time for establishing cell damage models were 200 µg/L AFB1 and 12 h for intestinal epithelium cells, 40 µg/L and 12 h for liver and kidney cells. Cell viabilities reached 231.58% (p < 0.05) for intestinal epithelium cells with CP addition, 105.29% and 115.84% (p < 0.05) for kidney and liver cells with CPS additions. The further results showed that intestinal epithelium, liver and kidney cell viabilities were significantly decreased to 87.12%, 88.7% and 84.19% (p < 0.05) when the cells were exposed to AFB1; however, they were increased to 93.49% by CPADE addition, 102.33% and 94.71% by CPSADE additions (p < 0.05). The relative mRNA abundances of IL-6, IL-8, TNF-α, iNOS, NF-κB, NOD1 (except liver cell) and TLR2 in three kinds of primary cells were significantly down-regulated by CPADE or CPSADE addition, compared with single AFB1 group (p < 0.05), indicating that CPADE or CPSADE addition could alleviate cell cytotoxicity and inflammation induced by AFB1 exposure through suppressing the activations of NF-κB, NOD1 and TLR2 pathways.

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Lycopene improves methotrexate-induced functional alterations of the Madin–Darby kidney cells in a concentration-dependent manner

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2019-0251 ◽

2020 ◽

Vol 98 (2) ◽

pp. 111-116

Author(s):

Nenad Stojiljković ◽

Sonja Ilić ◽

Nikola Stojanović ◽

Sanja Stojanović ◽

Milan Stoiljković

Keyword(s):

Cell Death ◽

Mdck Cell ◽

Kidney Injury ◽

Neutral Red ◽

High Dose ◽

Kidney Cells ◽

Dependent Manner ◽

High Concentration ◽

Concentration Dependent Manner ◽

Significant Impairment

Lycopene is one of the most potent antioxidants among carotenoids due to its ability to quench singlet oxygen and react with free radicals to reduce DNA damage. Methotrexate is widely used in the treatment of several types of cancers and autoimmune diseases. One of the most common side effects of a high-dose of methotrexate is kidney injury. In this study, we evaluated effects of lycopene on the Madin–Darby canine kidney cells (MDCK) treated with methotrexate through the estimation of their mitochondrial and lysosomal functions ((4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide reduction assay and neutral red uptake assay) and changes in cell oxidative status (determination of advanced oxidized proteins concentrations and reduced glutathione levels) and lysosomal enzymes activity (β-N-acetyl glucosaminidase activity). Results of our study showed that lycopene applied in high concentration caused significant impairment of the MDCK function leading to cell death. Contrarily, in relatively low concentrations lycopene moderately ameliorated methotrexate-induced MDCK cell death estimated by both biochemical and microscopic analyses. It also prevented a significant decline in the MDCK cell lysosomal function estimated by neutral red accumulation ability and activity of the lysosomal enzyme β-N-acetyl glucosaminidase.

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AGE-receptor-1 counteracts cellular oxidant stress induced by AGEs via negative regulation of p66shc-dependent FKHRL1 phosphorylation

AJP Cell Physiology ◽

10.1152/ajpcell.00350.2007 ◽

2008 ◽

Vol 294 (1) ◽

pp. C145-C152 ◽

Cited By ~ 74

Author(s):

Weijing Cai ◽

John Cijiang He ◽

Li Zhu ◽

Xue Chen ◽

Gary E. Striker ◽

...

Keyword(s):

Advanced Glycation End Products ◽

Oxidant Stress ◽

Serine Phosphorylation ◽

Hek293 Cells ◽

Antioxidant Defenses ◽

Kidney Cells ◽

Dependent Manner ◽

Advanced Glycation ◽

Glycation End Products ◽

End Products

Advanced glycation end products (AGEs) promote reactive oxygen species (ROS) formation and oxidant stress (OS) in diabetes and aging-related diseases. AGE-induced OS is suppressed by AGER1, an AGE-receptor that counteracts receptor for advanced glycation end products (RAGE) and epidermal growth factor receptor (EGFR)-mediated Shc/Ras signal activation, resulting in decreased OS. Akt, FKHRL1, and antioxidants; e.g., MnSOD, regulate OS. Serine phosphorylation of p66 shc also promotes OS. We examined the effects of two defined AGEs Nε-carboxy-methyl-lysine (CML) and methyl-glyoxal derivatives (MG) on these cellular pathways and their functional relationship to AGER1 in human embryonic kidney cells (HEK293). Stimulation of HEK293 cells with either AGE compound increased phosphorylation of Akt and FKHRL1 by approximately threefold in a redox-dependent manner. The use of p66 shc mutants showed that the AGE-induced effects required Ser-36 phosphorylation of p66 shc. AGE-induced phosphorylation of FKHRL1 led to a 70% downregulation of MnSOD, an effect partially blocked by a phosphatidylinositol 3-kinase inhibitor (LY-294002) and strongly inhibited by an antioxidant ( N-acetylcysteine). These pro-oxidant responses were suppressed in AGER1 overexpressing cells and reappeared when AGER1 expression was reduced by small interfering RNA (siRNA). These studies point to a new pathway for the induction of OS by AGEs involving FKHRL1 inactivation and MnSOD suppression via Ser-36 phosphorylation of p66 shc in human kidney cells. This represents a key mechanism by which AGER1 maintains cellular resistance against OS. Thus the decrease of AGER1 noted in aging and diabetes may further enhance OS and reduce innate antioxidant defenses.

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Elevated carbon dioxide upregulates NBCn1 Na+/HCO3− cotransporter in human embryonic kidney cells

AJP Renal Physiology ◽

10.1152/ajprenal.00096.2013 ◽

2013 ◽

Vol 305 (12) ◽

pp. F1765-F1774 ◽

Cited By ~ 4

Author(s):

Alejandro Orlowski ◽

Lorena A. Vargas ◽

Ernesto A. Aiello ◽

Bernardo V. Álvarez

Keyword(s):

Cell Types ◽

Recovery Phase ◽

Kidney Cells ◽

Dependent Manner ◽

Human Embryonic Kidney ◽

Human Embryonic Kidney Cells ◽

Hek Cells ◽

And Function ◽

Acid Loading ◽

Dose Dependent

The NBCn1 Na+/HCO3− cotransporter catalyzes the electroneutral movement of 1 Na+:1 HCO3− into kidney cells. We characterized the intracellular pH (pHi) regulation in human embryonic kidney cells (HEK) subjected to NH4Cl prepulse acid loading, and we examined the NBCn1 expression and function in HEK cells subjected to 24-h elevated Pco2 (10–15%). After acid loading, in the presence of HCO3−, ∼50% of the pHi recovery phase was blocked by the Na+/H+ exchanger inhibitors EIPA (10–50 μM) and amiloride (1 mM) and was fully cancelled by 30 μM EIPA under nominally HCO3−-free conditions. In addition, in the presence of HCO3−, pHi recovery after acid loading was completely blocked when Na+ was omitted in the buffer. pHi recovery after acidification in HEK cells was repeated in the presence of the NBC inhibitor S0859, and the pHi recovery was inhibited by S0859 in a dose-dependent manner ( Ki = 30 μM, full inhibition at 60 μM), which confirmed NBC Na+/HCO3− cotransporter activation. NBCn1 expression increased threefold after 24-h exposure of cultured HEK cells to 10% CO2 and sevenfold after exposure to 15% CO2, examined by immunoblots. Finally, exposure of HEK cells to high CO2 significantly increased the HCO3−-dependent recovery of pHi after acid loading. We conclude that HEK cells expressed the NBCn1 Na+/HCO3− cotransporter as the only HCO3−-dependent mechanism responsible for cellular alkaline loading. NBCn1, which expresses in different kidney cell types, was upregulated by 24-h high-Pco2 exposure of HEK cells, and this upregulation was accompanied by increased NBCn1-mediated HCO3− transport.

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Real-time monitoring of cadmium toxicity in rabbit kidney cells

Acta Veterinaria Brno ◽

10.2754/avb201584040351 ◽

2015 ◽

Vol 84 (4) ◽

pp. 351-356 ◽

Cited By ~ 3

Author(s):

Michal Milek ◽

Dana Marcinčáková ◽

Tomáš Csank ◽

Petra Kšonžeková ◽

Marcel Falis ◽

...

Keyword(s):

Toxic Effect ◽

Real Time ◽

Metabolic Activity ◽

Mtt Assay ◽

Metal Salt ◽

Cadmium Toxicity ◽

Rabbit Kidney ◽

Kidney Cells ◽

Dependent Manner ◽

Real Time Monitoring

The aim of this study was to investigate the toxic effect of the metal salt cadmium chloride dihydrate on the rabbit kidney cell line using the xCELLigence system or real-time cell analyser (RTCA), and to compare this relatively new method with standard biological cytotoxicity assays. This system provides real-time monitoring of cell behaviour and proliferative activity during the whole time of experiment. Moreover, after 24 h exposure of cells to cadmium, colorimetric 3-[4,5-dimethylthiazol-2-yl]-2,5-difenyl tetrazolium bromide (MTT) test was used to measure the metabolic activity and cytotoxicity was determined by measurement of lactate dehydrogenase (LDH) leaked from damaged cells. We found that renal cells exposed to lower concentrations (5–10 mg·l-1) of cadmium tend to grow similarly to control cells, however, cell index was significantly different (P < 0.05) after 24 h. With increasing concentration of cadmium (15–50 mg·l-1) significantly lower proliferative (P < 0.05) and metabolic activity (P < 0.05) of cells was observed and cytotoxicity increased simultaneously (P < 0.001). In addition, we found that the real-time monitoring of the cell response was significantly correlated with commonly used biological methods for toxicity measurement, for MTT assay R2 was 0.9448 (P < 0.01) and for LDH assay R2 was 0.9466 (P < 0.01), respectively. The present study is the first report when combination of RTCA, MTT assay and LDH test was used for cadmium nephrotoxicity assessment. In all these methods, the toxic effect of cadmium on rabbit kidney cells increased in a concentration-dependent manner.

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Effects of Low Molecular Weight Fibrinogen Degradation Products on Lymphocytes, Macrophages and Kidney Cells in Cultures

10.1055/s-0039-1687221 ◽

1979 ◽

Author(s):

M. Kopeć ◽

W. Rosazkowski ◽

S. Szmigielski ◽

B. Gerdin ◽

T. Saldeen

Keyword(s):

Degradation Products ◽

Biological Activities ◽

Peritoneal Macrophages ◽

Rabbit Kidney ◽

Low Molecular Weight ◽

Kidney Cells ◽

Dependent Manner ◽

Dose Dependent ◽

Mouse Peritoneal Macrophages ◽

Molecular Sieving

Dialysable peptides of mw 2200 to 3500 D(LMW-FDP) were isolated from products of exhaustive proteolysis of fibrinogen by plasmin. LMW-FDP inhibited in a dose dependent manner incorporation of 3H-thymidme into cultures of human blood lymphocytes simulated with PHA, concanavalin A or bacterial lipopolisaccharide. These effects were inversely related to stimulation indices. Phagocytosis of 3H-thymidine labelled Staphylococcus aureus by mouse peritoneal macrophages was also inhibited by LMW-FDP. These peptides induced a cytotoxic effect on continuous line of rabbit kidney cells in cultures as manifested by inhibition of 86Rb and 3H-incorporation as well as by releese of 86Rb and 61Cr from prelabelled cells. Eight fractions obtained by molecular sieving of LMW - FDP on Bio-Gel P-6 columns were found to differ pronouncedly in biological activities.

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