scholarly journals Penicilliumin B Protects against Cisplatin-Induced Renal Tubular Cell Apoptosis through Activation of AMPK-Induced Autophagy and Mitochondrial Biogenesis

2021 ◽  
pp. 1-15
Author(s):  
Weiwei Shen ◽  
Nan Jia ◽  
Jinhua Miao ◽  
Shuangqin Chen ◽  
Shan Zhou ◽  
...  
Keyword(s):  
Mitochondrial Biogenesis ◽  
Cell Apoptosis ◽  
Cell Injury ◽  
Protective Role ◽  
Tubular Cell ◽  
Mitochondrial Morphology ◽  
Autophagic Flux ◽  
Renal Tubular Cell ◽  
Compound C ◽  
Renal Tubular

<b><i>Introduction:</i></b> Acute kidney injury (AKI) is at a high prevalence in hospitalized patients, especially in those receiving chemotherapy. Cisplatin is the most widely used chemotherapy drug; however, with its side effects that include nephrotoxicity, it also exhibits a risk of inducing AKI. Importantly, recent studies have shown that autophagy plays a protective role in cisplatin-induced AKI. However, therapeutic strategies and candidate drugs for inducing activation of autophagy remain limited. <b><i>Methods:</i></b> In the present study, we adopted a novel candidate drug from a deep sea-derived <i>Penicillium</i> strain, penicilliumin B, to testify its protective role in cisplatin-induced renal tubular cell injury. <b><i>Results:</i></b> Penicilliumin B exhibited protection against cisplatin-induced apoptosis in cultured renal tubular epithelial cells and in cisplatin-treated mice. Moreover, penicilliumin B maintained normal mitochondrial morphology and inhibited the production of mitochondrial reactive oxygen species. Further studies demonstrated that penicilliumin B enhanced autophagic flux, promoted the activation of multiple autophagy-related proteins, such as mTOR, Beclin-1, ATG5, PINK1, and LC3B, and induced the degradation of p62. Interestingly, we also found penicilliumin B triggered phosphorylation of adenosine 5‘-monophosphate-activated protein kinase (AMPK), which is an upstream inducer of nearly all autophagy pathways and also an activator of mitochondrial biogenesis. These results suggest that AMPK may represent an activated site of penicilliumin B. Consistently, compound C, an AMPK inhibitor, significantly blocked the protective effects of penicilliumin B on mitochondria and apoptotic inhibition. <b><i>Conclusion:</i></b> Taken together, our findings indicate that penicilliumin B represents a novel AMPK activator that may provide protection against renal tubular cell apoptosis through activation of AMPK-induced autophagy and mitochondrial biogenesis.

scholarly journals NIX-mediated mitophagy protects against proteinuria-induced tubular cell apoptosis and renal injury

2019 ◽  
Vol 316 (2) ◽  
pp. F382-F395 ◽  
Author(s):  
Dan Xu ◽  
Panpan Chen ◽  
Bao Wang ◽  
Yanzhe Wang ◽  
Naijun Miao ◽  
...  
Keyword(s):  
Renal Injury ◽  
Cell Apoptosis ◽  
Cell Injury ◽  
Kidney Injury ◽  
Underlying Mechanism ◽  
Tubular Cell ◽  
Renal Tubular Cell ◽  
Common Symptom ◽  
Renal Tubules ◽  
Renal Tubular

Proteinuria, the most common symptom of renal injury, is an independent factor for renal tubular injury. However, the underlying mechanism remains to be fully elucidated. Mitochondrion is an important target for proteinuria-induced renal tubular cell injury. Insufficient mitophagy exacerbates cell injury by initiating mitochondrial dysfunction-related cell apoptosis. In the experiment, the role of NIP3-like protein X (NIX)-mediated mitophagy was investigated in proteinuria-induced renal injury. In this study, we demonstrated that NIX expression was reduced in renal tubules and correlated with the decline of estimated glomerular filtration rate and increase of the proteinuria in patients. In proteinuric mice, NIX-mediated mitophagy was significantly suppressed. Meanwhile, the proteinuric mice exhibited renal dysfunction, increased mitochondrial fragmentation, and tubular cell apoptosis. Overexpression of NIX attenuated those disruptions in proteinuric mice. In cultured renal tubular epithelial cells, albumin induced a decrease in NIX-mediated mitophagy and an increase in cell apoptosis. Overexpression of NIX attenuated albumin-induced cell apoptosis, whereas NIX siRNA aggravated these perturbations. These results indicate that proteinuria suppresses NIX-mediated mitophagy in the renal tubular epithelial cell, which triggers the cell undergoing mitochondria-dependent cell apoptosis. Collectively, our finding suggests that restoration of NIX-mediated mitophagy might be a novel therapeutic target for alleviating proteinuria-induced kidney injury.

Propylene glycol-induced proximal renal tubular cell injury

1997 ◽  
Vol 30 (1) ◽  
pp. 134-139 ◽  
Author(s):  
Peter D. Yorgin ◽  
Andreas A. Theodorou ◽  
Amira Al-Uzri ◽  
Karen Davenport ◽  
Leslie V. Boyer-Hassen ◽  
...  
Keyword(s):  
Propylene Glycol ◽  
Cell Injury ◽  
Tubular Cell ◽  
Renal Tubular Cell ◽  
Renal Tubular

scholarly journals Protection Against Cold Storage–Induced Renal Tubular Cell Apoptosis

2015 ◽  
Vol 99 (11) ◽  
pp. 2311-2316 ◽  
Author(s):  
Swati Jain ◽  
Daniel Keys ◽  
Danica Ljubanovic ◽  
Charles L. Edelstein ◽  
Alkesh Jani
Keyword(s):  
Cold Storage ◽  
Cell Apoptosis ◽  
Tubular Cell ◽  
Renal Tubular Cell ◽  
Renal Tubular

scholarly journals HIF-1-mediated production of exosomes during hypoxia is protective in renal tubular cells

2017 ◽  
Vol 313 (4) ◽  
pp. F906-F913 ◽  
Author(s):  
Wei Zhang ◽  
Xiangjun Zhou ◽  
Qisheng Yao ◽  
Yutao Liu ◽  
Hao Zhang ◽  
...  
Keyword(s):  
Cell Injury ◽  
Hypoxia Inducible Factor ◽  
Atp Depletion ◽  
Tubular Cell ◽  
Renal Tubular Cell ◽  
Dependent Manner ◽  
Protective Effects ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Renal Tubular

Exosomes are nano-sized vesicles produced and secreted by cells to mediate intercellular communication. The production and function of exosomes in kidney tissues and cells remain largely unclear. Hypoxia is a common pathophysiological condition in kidneys. This study was designed to characterize exosome production during hypoxia of rat renal proximal tubular cells (RPTCs), investigate the regulation by hypoxia-inducible factor-1 (HIF-1), and determine the effect of the exosomes on ATP-depletion-induced tubular cell injury. Hypoxia did not change the average sizes of exosomes secreted by RPTCs, but it significantly increased exosome production in a time-dependent manner. HIF-1 induction with dimethyloxalylglycine also promoted exosome secretion, whereas pharmacological and genetic suppression of HIF-1 abrogated the increase of exosome secretion under hypoxia. The exosomes from hypoxic RPTCs had inhibitory effects on apoptosis of RPTCs following ATP depletion. The protective effects were lost in the exosomes from HIF-1α knockdown cells. It is concluded that hypoxia stimulates exosome production and secretion in renal tubular cells. The exosomes from hypoxic cells are protective against renal tubular cell injury. HIF-1 mediates exosome production during hypoxia and contributes to the cytoprotective effect of the exosomes.

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 Growth arrest and DNA damage 45γ is required for caspase-dependent renal tubular cell apoptosis

PLoS ONE ◽  
2019 ◽  
Vol 14 (2) ◽  
pp. e0212818
Author(s):  
Gyu-Tae Shin ◽  
Hwa Joung Lee ◽  
Ji Eun Park
Keyword(s):  
Dna Damage ◽  
Cell Apoptosis ◽  
Growth Arrest ◽  
Tubular Cell ◽  
Renal Tubular Cell ◽  
Renal Tubular

A14340 Endothelial dysfunction exacerbates renal tubular cell injury through inflammasome activation in hypertensive model mice

2018 ◽  
Vol 36 ◽  
pp. e76
Author(s):  
Nagasu Hajime ◽  
Kengo Kidokoro ◽  
Minoru Satoh ◽  
Seiji Itano ◽  
Tamaki Sasaki ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Cell Injury ◽  
Tubular Cell ◽  
Inflammasome Activation ◽  
Renal Tubular Cell ◽  
Renal Tubular
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