scholarly journals Role of Intracellular Ca2+and Na+/Ca2+Exchanger in the Pathogenesis of Contrast-Induced Acute Kidney Injury

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Dingping Yang ◽  
Dingwei Yang
Keyword(s):  
Acute Kidney Injury ◽  
Cell Injury ◽  
Kidney Injury ◽  
Renal Tubular Cell ◽  
Voltage Dependent ◽  
Key Factor ◽  
Intracellular Ca ◽  
Underlying Mechanisms ◽  
Renal Tubular

The precise mechanisms underlying contrast-induced acute kidney injury (CI-AKI) are not well understood. Intracellular Ca2+overload is considered to be a key factor in CI-AKI. Voltage-dependent Ca2+channel (VDC) and Na+/Ca2+exchanger (NCX) system are the main pathways of intracellular Ca2+overload in pathological conditions. Here, we review the potential underlying mechanisms involved in CI-AKI and discuss the role of NCX-mediated intracellular Ca2+overload in the contrast media-induced renal tubular cell injury and renal hemodynamic disorder.

miR-30e-5p regulates autophagy and apoptosis by targeting Beclin1 involved in contrast-induced acute kidney injury

2021 ◽  
Vol 28 ◽  
Author(s):  
Xiaoqin Liu ◽  
Qingzhao Li ◽  
Lixin Sun ◽  
Limei Chen ◽  
Yue Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Kidney Injury ◽  
Cell Apoptosis ◽  
Cell Injury ◽  
Cell Model ◽  
Kidney Injury ◽  
Cell Vitality ◽  
A Cell ◽  
Renal Tubular ◽  
Induced Apoptosis

Aims: This study aims to verify if miR-30e-5p targets Beclin1 (BECN1), a key regulator of autophagy, and investigate the function of miR-30e-5p and Beclin1 through mediating autophagy and apoptosis in contrast-induced acute kidney injury (CI-AKI). Methods: Human renal tubular epithelial HK-2 cells were treated with Urografin to construct a cell model of CI-AKI. Real-time reverse transcription–polymerase chain reaction was used to detect gene expression. The dual-luciferase reporting assay and endogenous validation were used to verify targeting and regulating function. The expressions of protein were detected using Western blot. Cell proliferation was detected using methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. Cell apoptosis was detected using terminal-deoxynucleoitidyl transferase mediated nick end labeling assay, and autophagy was detected using transmission electron microscopy. Results: HK-2 cells exposed to Urografin for 2 h induced a significant increase in miR-30e-5p. miR-30e-5p had a targeting effect on Beclin1. Moreover, Urografin exposure can enhance cell apoptosis by increasing caspase 3 gene expression and inhibiting autophagy, which was induced by decreased Beclin1 expression regulated by miR-30e-5p, thereby resulting in renal cell injury. Downregulation of miR-30e-5p or upregulation of Beclin1 restored cell vitality by promoting autophagy and suppressing apoptosis in Urografin-treated cells. Conclusions: Urografin increased the expression of miR-30e-5p in HK-2 cells and thus decreased Beclin1 levels to inhibit autophagy, but induced apoptosis, which may be the mechanism for CI-AKI.

scholarly journals Class IIa HDAC inhibitor TMP195 alleviates lipopolysaccharide-induced acute kidney injury

2020 ◽  
Vol 319 (6) ◽  
pp. F1015-F1026
Author(s):  
Wei Zhang ◽  
Yinjie Guan ◽  
George Bayliss ◽  
Shougang Zhuang
Keyword(s):  
Acute Kidney Injury ◽  
Hdac Inhibitor ◽  
Cell Apoptosis ◽  
Kidney Injury ◽  
Tubular Cell ◽  
Intercellular Adhesion Molecule ◽  
Renal Tubular Cell ◽  
Renoprotective Effect ◽  
Renal Tubular ◽  
Class Iia Hdacs

Sepsis-associated acute kidney injury (SA-AKI) is associated with high mortality rates, but clinicians lack effective treatments except supportive care or renal replacement therapies. Recently, histone deacetylase (HDAC) inhibitors have been recognized as potential treatments for acute kidney injury and sepsis in animal models; however, the adverse effect generated by the use of pan inhibitors of HDACs may limit their application in people. In the present study, we explored the possible renoprotective effect of a selective class IIa HDAC inhibitor, TMP195, in a murine model of SA-AKI induced by lipopolysaccharide (LPS). Administration of TMP195 significantly reduced increased serum creatinine and blood urea nitrogen levels and renal damage induced by LPS; this was coincident with reduced expression of HDAC4, a major isoform of class IIa HDACs, and elevated histone H3 acetylation. TMP195 treatment following LPS exposure also reduced renal tubular cell apoptosis and attenuated renal expression of neutrophil gelatinase-associated lipocalin and kidney injury molecule-1, two biomarkers of tubular injury. Moreover, LPS exposure resulted in increased expression of BAX and cleaved caspase-3 and decreased expression of Bcl-2 and bone morphogenetic protein-7 in vivo and in vitro; TMP195 treatment reversed these responses. Finally, TMP195 inhibited LPS-induced upregulation of multiple proinflammatory cytokines/chemokines, including intercellular adhesion molecule-1, monocyte chemoattractant protein-1, tumor necrosis factor-α, and interleukin-1β, and accumulation of inflammatory cells in the injured kidney. Collectively, these data indicate that TMP195 has a powerful renoprotective effect in SA-AKI by mitigating renal tubular cell apoptosis and inflammation and suggest that targeting class IIa HDACs might be a novel therapeutic strategy for the treatment of SA-AKI that avoids the unintended adverse effects of a pan-HDAC inhibitor.

scholarly journals Stanniocalcin-1 Alleviates Contrast-Induced Acute Kidney Injury by Regulating Mitochondrial Quality Control via the Nrf2 Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-17 ◽  
Author(s):  
Fei Zhao ◽  
Li-Xin Feng ◽  
Qian Liu ◽  
Hong-Shen Wang ◽  
Cheng-Yuan Tang ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Quality Control ◽  
Kidney Injury ◽  
Protective Role ◽  
Mitochondrial Quality Control ◽  
Therapy Strategy ◽  
Nrf2 Signaling Pathway ◽  
Short And Long Term ◽  
Renal Tubular

Contrast-induced acute kidney injury (CI-AKI) is the third common cause of acute kidney injury (AKI), which is associated with poor short- and long-term outcomes. Currently, effective therapy strategy for CI-AKI remains lacking. Stanniocalcin-1 (STC1) is a conserved glycoprotein with antiapoptosis and anti-inflammatory functions, but the role of STC1 in controlling CI-AKI is unknown. Here, we demonstrated a protective role of STC1 in contrast-induced injury in cultured renal tubular epithelial cells and CI-AKI rat models. Recombinant human STC1 (rhSTC1) regulated mitochondrial quality control, thus suppressing contrast-induced mitochondrial damage, oxidative stress, inflammatory response, and apoptotic injury. Mechanistically, activation of the Nrf2 signaling pathway contributes critically to the renoprotective effect of STC1. Together, this study demonstrates a novel role of STC1 in preventing CI-AKI and reveals Nrf2 as a molecular target of STC1. Therefore, this study provides a promising preventive target for the treatment of CI-AKI.

scholarly journals The Predictive Role of the Biomarker Kidney Molecule-1 (KIM-1) in Acute Kidney Injury (AKI) Cisplatin-Induced Nephrotoxicity

2019 ◽  
Vol 20 (20) ◽  
pp. 5238 ◽  
Author(s):  
Daniela Maria Tanase ◽  
Evelina Maria Gosav ◽  
Smaranda Radu ◽  
Claudia Florida Costea ◽  
Manuela Ciocoiu ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Injury ◽  
In Vivo Studies ◽  
Renal Tubular Cells ◽  
Renal Tubular ◽  
Induced Apoptosis ◽  
Kidney Injury Molecule 1

Acute kidney injury (AKI) following platinum-based chemotherapeutics is a frequently reported serious side-effect. However, there are no approved biomarkers that can properly identify proximal tubular injury while routine assessments such as serum creatinine lack sensitivity. Kidney-injury-molecule 1 (KIM-1) is showing promise in identifying cisplatin-induced renal injury both in vitro and in vivo studies. In this review, we focus on describing the mechanisms of renal tubular cells cisplatin-induced apoptosis, the associated inflammatory response and oxidative stress and the role of KIM-1 as a possible biomarker used to predict cisplatin associated AKI.

scholarly journals C-type lectin Mincle mediates cell death–triggered inflammation in acute kidney injury

2020 ◽  
Vol 217 (11) ◽  
Author(s):  
Miyako Tanaka ◽  
Marie Saka-Tanaka ◽  
Kozue Ochi ◽  
Kumiko Fujieda ◽  
Yuki Sugiura ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Cell Death ◽  
Free Cholesterol ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Sterile Inflammation ◽  
Renal Tubular Cell ◽  
Renal Tubules ◽  
Underlying Mechanisms

Accumulating evidence indicates that cell death triggers sterile inflammation and that impaired clearance of dead cells causes nonresolving inflammation; however, the underlying mechanisms are still unclear. Here, we show that macrophage-inducible C-type lectin (Mincle) senses renal tubular cell death to induce sustained inflammation after acute kidney injury in mice. Mincle-deficient mice were protected against tissue damage and subsequent atrophy of the kidney after ischemia–reperfusion injury. Using lipophilic extract from the injured kidney, we identified β-glucosylceramide as an endogenous Mincle ligand. Notably, free cholesterol markedly enhanced the agonistic effect of β-glucosylceramide on Mincle. Moreover, β-glucosylceramide and free cholesterol accumulated in dead renal tubules in proximity to Mincle-expressing macrophages, where Mincle was supposed to inhibit clearance of dead cells and increase proinflammatory cytokine production. This study demonstrates that β-glucosylceramide in combination with free cholesterol acts on Mincle as an endogenous ligand to induce cell death–triggered, sustained inflammation after acute kidney injury.

scholarly journals Cytokine cooperation in renal tubular cell injury: The role of TWEAK

2006 ◽  
Vol 70 (10) ◽  
pp. 1750-1758 ◽  
Author(s):  
P. Justo ◽  
A.B. Sanz ◽  
M.D. Sanchez-Niño ◽  
J.A. Winkles ◽  
C. Lorz ◽  
...  
Keyword(s):  
Cell Injury ◽  
Tubular Cell ◽  
Renal Tubular Cell ◽  
Renal Tubular

scholarly journals Amphotericin B-Induced Renal Tubular Cell Injury Is Mediated by Na+ Influx through Ion-Permeable Pores and Subsequent Activation of Mitogen-Activated Protein Kinases and Elevation of Intracellular Ca2+ Concentration

2009 ◽  
Vol 53 (4) ◽  
pp. 1420-1426 ◽  
Author(s):  
Takahisa Yano ◽  
Yoshinori Itoh ◽  
Eiko Kawamura ◽  
Asuka Maeda ◽  
Nobuaki Egashira ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Map Kinases ◽  
Cell Injury ◽  
Kinase Inhibitor ◽  
Tubular Cell ◽  
Membrane Cholesterol ◽  
Renal Tubular Cell ◽  
Mitogen Activated Protein ◽  
Intracellular Ca ◽  
Renal Tubular

ABSTRACT Amphotericin B (AMB) is one of the most effective antifungal agents; however, its use is often limited by the occurrence of adverse events, especially nephrotoxicity. The present study was designed to determine the possible mechanisms underlying the nephrotoxic action of AMB. The exposure of a porcine proximal renal tubular cell line (LLC-PK1 cells) to AMB caused cell injury, as assessed by mitochondrial enzyme activity, the leakage of lactate dehydrogenase, and tissue ATP depletion. Propidium iodide uptake was enhanced, while terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling was not affected by AMB, suggesting a lack of involvement of apoptosis in AMB-induced cell injury. The cell injury was inhibited by the depletion of membrane cholesterol with methyl-β-cyclodextrin, which lowered the extracellular Na+ concentration or the chelation of intracellular Ca2+. The rise in the intracellular Ca2+ concentration may be mediated through the activation of the ryanodine receptor (RyR) on the endoplasmic reticulum and the mitochondrial Na+-Ca2+ exchanger, since cell injury was attenuated by dantrolene (an RyR antagonist) and CGP37157 (an Na+-Ca2+ exchanger inhibitor). Moreover, AMB-induced cell injury was reversed by PD169316 (a p38 mitogen-activated protein [MAP] kinase inhibitor), c-Jun N-terminal kinase inhibitor II, and PD98059 (a MEK1/2 inhibitor). The phosphorylations of these MAP kinases were enhanced by AMB in a calcium-independent manner, suggesting the involvement of MAP kinases in AMB-induced cell injury. These findings suggest that Na+ entry through membrane pores formed by the association of AMB with membrane cholesterol leads to the activation of MAP kinases and the elevation of the intracellular Ca2+ concentration, leading to renal tubular cell injury.

scholarly journals p53-cyclophilin D mediates renal tubular cell apoptosis in ischemia-reperfusion-induced acute kidney injury

2019 ◽  
Vol 317 (5) ◽  
pp. F1311-F1317 ◽  
Author(s):  
Huan Yang ◽  
Ruizhao Li ◽  
Li Zhang ◽  
Shu Zhang ◽  
Wei Dong ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Cell Death ◽  
Cell Apoptosis ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Tubular Cell ◽  
Renal Tubular Cell ◽  
Cyclophilin D ◽  
Mptp Opening ◽  
Renal Tubular

Ischemia-reperfusion (I/R)-induced acute kidney injury (I/R-AKI) favors mitochondrial permeability transition pore (mPTP) opening and subsequent cell death. Cyclophilin D (CypD) is an essential component of the mPTP, and recent findings have implicated the p53-CypD complex in cell death. To evaluate the role of p53-CypD after I/R-AKI, we tested the hypothesis that the p53-CypD complex mediates renal tubular cell apoptosis in I/R-AKI via mPTP opening. Expression of p53 and cleaved caspase-3 was significantly increased in rats subjected to I/R-AKI compared with normal controls and sham-operated controls. The underlying mechanisms were determined using an in vitro model of ATP depletion. Inhibition of mPTP opening using the CypD inhibitor cyclosporin A or siRNA for p53 in ATP-depleted HK-2 cells prevented mitochondrial membrane depolarization and reduced apoptosis. Furthermore, p53 bound to CypD in ATP-depleted HK-2 cells. These results suggest that the p53-CypD complex mediates renal tubular cell apoptosis in I/R-AKI via mPTP opening.

scholarly journals Glycogen Synthase Kinase-3 Signaling in Acute Kidney Injury

Nephron ◽  
2020 ◽  
Vol 144 (12) ◽  
pp. 609-612
Author(s):  
Abeda Jamadar ◽  
Reena Rao
Keyword(s):  
Acute Kidney Injury ◽  
Molecular Mechanisms ◽  
Glycogen Synthase ◽  
Kidney Injury ◽  
Tubular Epithelial Cell ◽  
Clinical Syndrome ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Renal Tubular

Acute kidney injury (AKI) is a common clinical syndrome that involves renal tubular epithelial cell death and leads to acute decline in renal function. Improper tubular regeneration following AKI often leads to CKD. We discuss the role of a serine/threonine protein kinase called glycogen synthase kinase-3 (GSK3) in renal tubular injury and renal fibrosis. We also highlight the importance of GSK3 as a potential drug target in AKI patients and molecular mechanisms promoting tissue regeneration.

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