scholarly journals Augmentation of Glucotoxicity, Oxidative Stress, Apoptosis and Mitochondrial Dysfunction in HepG2 Cells by Palmitic Acid

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1979 ◽  
Author(s):  
Arwa Alnahdi ◽  
Annie John ◽  
Haider Raza
Keyword(s):  
Oxidative Stress ◽  
Cell Signaling ◽  
Palmitic Acid ◽  
Mitochondrial Dysfunction ◽  
Stress Responses ◽  
High Glucose ◽  
Hepg2 Cells ◽  
High Energy ◽  
Redox Stress ◽  
Energy Metabolites

Hyperglycemia and hyperlipidemia are the hallmarks of diabetes and obesity. Experimental and epidemiological studies have suggested that dietary management and caloric restriction are beneficial in reducing the complications of diabesity. Studies have suggested that increased availability of energy metabolites like glucose and saturated fatty acids induces metabolic, oxidative, and mitochondrial stress, accompanied by inflammation that may lead to chronic complications in diabetes. In the present study, we used human hepatoma HepG2 cells to investigate the effects of high glucose (25 mM) and high palmitic acid (up to 0.3 mM) on metabolic-, inflammatory-, and redox-stress-associated alterations in these cells. Our results showed increased lipid, protein, and DNA damage, leading to caspase-dependent apoptosis and mitochondrial dysfunction. Glucolipotoxicity increased ROS production and redox stress appeared to alter mitochondrial membrane potential and bioenergetics. Our results also demonstrate the enhanced ability of cytochrome P450s-dependent drug metabolism and antioxidant adaptation in HepG2 cells treated with palmitic acid, which was further augmented with high glucose. Altered NF-kB/AMPK/mTOR-dependent cell signaling and inflammatory (IL6/TNF-α) responses were also observed. Our results suggest that the presence of high-energy metabolites enhances apoptosis while suppressing autophagy by inducing inflammatory and oxidative stress responses that may be responsible for alterations in cell signaling and metabolism.

scholarly journals Mitigation of Glucolipotoxicity-Induced Apoptosis, Mitochondrial Dysfunction, and Metabolic Stress by N-Acetyl Cysteine in Pancreatic β-Cells

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 239 ◽  
Author(s):  
Arwa Alnahdi ◽  
Annie John ◽  
Haider Raza
Keyword(s):  
Energy Metabolism ◽  
Palmitic Acid ◽  
Mitochondrial Dysfunction ◽  
High Glucose ◽  
High Energy ◽  
Metabolic Adaptation ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Mitochondrial Energy Metabolism ◽  
Acetyl Cysteine

Glucolipotoxicity caused by hyperglycemia and hyperlipidemia are the common features of diabetes-induced complications. Metabolic adaptation, particularly in energy metabolism; mitochondrial dysfunction; and increased inflammatory and oxidative stress responses are considered to be the main characteristics of diabetes and metabolic syndrome. However, due to various fluctuating endogenous and exogenous stimuli, the precise role of these factors under in vivo conditions is not clearly understood. In the present study, we used pancreatic β-cells, Rin-5F, to elucidate the molecular and metabolic changes in glucolipotoxicity. Cells treated with high glucose (25 mM) and high palmitic acid (up to 0.3 mM) for 24 h exhibited increased caspase/poly-ADP ribose polymerase (PARP)-dependent apoptosis followed by DNA fragmentation, alterations in mitochondrial membrane permeability, and bioenergetics, accompanied by alterations in glycolytic and mitochondrial energy metabolism. Our results also demonstrated alterations in the expression of mammalian target of rapamycin (mTOR)/5′ adenosine monophosphate-activated protein kinase (AMPK)-dependent apoptotic and autophagy markers. Furthermore, pre-treatment of cells with 10 mM N-acetyl cysteine attenuated the deleterious effects of high glucose and high palmitic acid with improved cellular functions and survival. These results suggest that the presence of high energy metabolites enhance mitochondrial dysfunction and apoptosis by suppressing autophagy and adapting energy metabolism, mediated, at least in part, via enhanced oxidative DNA damage and mTOR/AMPK-dependent cell signaling.

scholarly journals The Role of the Antioxidant Response in Mitochondrial Dysfunction in Degenerative Diseases: Cross-Talk between Antioxidant Defense, Autophagy, and Apoptosis

2019 ◽  
Vol 2019 ◽  
pp. 1-26 ◽  
Author(s):  
Michael L.-H. Huang ◽  
Shannon Chiang ◽  
Danuta S. Kalinowski ◽  
Dong-Hun Bae ◽  
Sumit Sahni ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Dynamics ◽  
Signal Transmission ◽  
Antioxidant Response ◽  
High Energy ◽  
Stress Factors ◽  
Degenerative Diseases ◽  
Energy Demands ◽  
Stress Energy

The mitochondrion is an essential organelle important for the generation of ATP for cellular function. This is especially critical for cells with high energy demands, such as neurons for signal transmission and cardiomyocytes for the continuous mechanical work of the heart. However, deleterious reactive oxygen species are generated as a result of mitochondrial electron transport, requiring a rigorous activation of antioxidative defense in order to maintain homeostatic mitochondrial function. Indeed, recent studies have demonstrated that the dysregulation of antioxidant response leads to mitochondrial dysfunction in human degenerative diseases affecting the nervous system and the heart. In this review, we outline and discuss the mitochondrial and oxidative stress factors causing degenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, Huntington’s disease, and Friedreich’s ataxia. In particular, the pathological involvement of mitochondrial dysfunction in relation to oxidative stress, energy metabolism, mitochondrial dynamics, and cell death will be explored. Understanding the pathology and the development of these diseases has highlighted novel regulators in the homeostatic maintenance of mitochondria. Importantly, this offers potential therapeutic targets in the development of future treatments for these degenerative diseases.

Deoxyelephantopin induces apoptosis in HepG2 cells via oxidative stress, NF-κB inhibition and mitochondrial dysfunction

BioFactors ◽  
2016 ◽  
Vol 43 (1) ◽  
pp. 63-72 ◽  
Author(s):  
Tahir Mehmood ◽  
Amara Maryam ◽  
He Zhang ◽  
Yongming Li ◽  
Muhammad Khan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Hepg2 Cells

scholarly journals Pyrrolidine Dithiocarbamate (PDTC) Inhibits DON-Induced Mitochondrial Dysfunction and Apoptosis via the NF-κB/iNOS Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Dan Wan ◽  
Qinghua Wu ◽  
Wei Qu ◽  
Gang Liu ◽  
Xu Wang
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Stress Responses ◽  
Cell Types ◽  
Gh3 Cells ◽  
Pyrrolidine Dithiocarbamate ◽  
Protective Effects ◽  
Morphological Studies ◽  
Transmission Electron ◽  
Toxic Responses

Oxidative stress is closely linked to the toxic responses of various cell types in normal and pathophysiological conditions. Deoxynivalenol (DON), an inducer of stress responses in the ribosome and the endoplasmic reticulum (ER), causes mitochondrial dysfunction and mitochondria-dependent apoptosis through oxidative stress in humans and animals. The NF-κB pathway, which is closely linked to oxidative stress, is hypothesized to be a critical signaling pathway for DON-induced toxicity and is a potential target for intervention. The present study was conducted to explore the protective effects of pyrrolidine dithiocarbamate (PDTC) from the toxic effects of DON in rat anterior pituitary GH3 cells. Our results showed that DON activated the NF-κB transcription factors and induced cellular oxidative stress, mitochondrial dysfunction, and apoptosis. Morphological studies using transmission electron microscopy (TEM) and cell apoptosis analyses suggested that PDTC prevented DON-induced mitochondrial dysfunction and apoptosis, probably by preventing the DON-induced translocation of NF-κB p65 into the nucleus, and by inhibiting DON-induced iNOS expression. This led to the blocking of the NF-κB pathway and inhibition of iNOS activity.

scholarly journals Ellagic acid ameliorates oxidative stress and insulin resistance in high glucose-treated HepG2 cells via miR-223/keap1-Nrf2 pathway

2019 ◽  
Vol 110 ◽  
pp. 85-94 ◽  
Author(s):  
Xiaoqin Ding ◽  
Tunyu Jian ◽  
Yuexian Wu ◽  
Yuanyuan Zuo ◽  
Jiawei Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
High Glucose ◽  
Ellagic Acid ◽  
Hepg2 Cells ◽  
Nrf2 Pathway

scholarly journals CGRP Reduces Apoptosis of DRG Cells Induced by High-Glucose Oxidative Stress Injury through PI3K/AKT Induction of Heme Oxygenase-1 and Nrf-2 Expression

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
YaDong Liu ◽  
SiCong Zhang ◽  
Jun Xue ◽  
ZhongQing Wei ◽  
Ping Ao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Responses ◽  
High Glucose ◽  
Structural Characteristics ◽  
Akt Pathway ◽  
Heme Oxygenase 1 ◽  
Phosphatidylinositol 3 Kinase ◽  
Stress Injury ◽  
Culture Model ◽  
Diabetic Bladder

Dorsal root ganglion (DRG) neurons, which are sensitive to oxidative stress due to their anatomical and structural characteristics, play a complex role in the initiation and progression of diabetic bladder neuropathy. We investigated the hypothesis that the antioxidant and antiapoptotic effects of CGRP may be partly related to the expression of Nrf2 and HO-1, via the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, thus reducing apoptosis and oxidative stress responses. This study shows that CGRP activates the PI3K/AKT pathway, thereby inducing increased expression of Nrf2 and HO-1 and resulting in the decrease of reactive oxygen species and malondialdehyde levels and reduced neuronal apoptosis. These effects were suppressed by LY294002, an inhibitor of the PI3K/AKT pathway. Therefore, regulation of Nrf2 and HO-1 expression by the PI3K/AKT pathway plays an important role in the regulation of the antioxidant and antiapoptotic responses in DRG cells in a high-glucose culture model.

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