scholarly journals Organic Dust Exposure Induces Stress Response and Mitochondrial Dysfunction in Monocytic Cells

2020 ◽  
Author(s):  
Sanjana Mahadev-Bhat ◽  
Denusha Shrestha ◽  
Nyzil Massey ◽  
Locke A. Karriker ◽  
Anumantha G. Kanthasamy ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Cell Viability ◽  
Mitochondrial Dysfunction ◽  
Inflammatory Responses ◽  
Ethyl Pyruvate ◽  
Dust Exposure ◽  
Organic Dust ◽  
Cytochrome C Release ◽  
Monocytic Cell ◽  
Functional Changes

AbstractExposure to airborne organic dust (OD), rich in microbial pathogen-associated molecular patterns, has been shown to induce inflammatory responses in the lung resulting in changes in airway structure and function. A common manifestation in lung inflammation is the occurrence of altered mitochondrial structure and bioenergetics, consequently regulating mitochondrial ROS (mROS) and creating a vicious cycle of mitochondrial dysfunction.The role of mitochondrial dysfunction in airway diseases such as COPD and asthma is well known. However, whether OD exposure induces mitochondrial dysfunction largely remains unknown. Therefore, in this study, we tested a hypothesis that OD exposure induces mitochondrial stress using a human monocytic cell line (THP-1). We examined the mechanisms of organic dust extract (ODE) exposure-induced mitochondrial structural and functional changes in THP-1 cells.In addition, the effect of co-exposure to ethyl pyruvate (EP), a known anti-inflammatory agent, or mitoapocynin (MA), a mitochondria targeting NOX2 inhibitor was examined. Transmission electron microscopy images showed significant changes in cellular and organelle morphology upon ODE exposure. ODE exposure with and without EP co-treatment increased the mtDNA leakage into the cytosol. Next, ODE exposure increased the PINK1 and Parkin expression, cytoplasmic cytochrome c levels and reduced mitochondrial mass and cell viability, indicating mitophagy. MA treatment was partially protective by decreasing Parkin expression, mtDNA and cytochrome c release and increasing cell viability.

scholarly journals High-Dialysate-Glucose-Induced Oxidative Stress and Mitochondrial-Mediated Apoptosis in Human Peritoneal Mesothelial Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Kuan-Yu Hung ◽  
Shin-Yun Liu ◽  
Te-Cheng Yang ◽  
Tien-Ling Liao ◽  
Shu-Huei Kao
Keyword(s):  
Cell Death ◽  
Mitochondrial Dysfunction ◽  
Mesothelial Cells ◽  
Cytochrome C Release ◽  
Dialysis Adequacy ◽  
Peritoneal Mesothelial Cells ◽  
Functional Changes ◽  
Key Factor ◽  
Human Peritoneal Mesothelial Cells ◽  
Induced Apoptosis

Human peritoneal mesothelial cells (HPMCs) are a critical component of the peritoneal membrane and play a pivotal role in dialysis adequacy. Loss of HPMCs can contribute to complications in peritoneal dialysis. Compelling evidence has shown that high-dialysate glucose is a key factor causing functional changes and cell death in HPMCs. We investigated the mechanism of HPMC apoptosis induced by high-dialysate glucose, particularly the role of mitochondria in the maintenance of HPMCs. HPMCs were incubated at glucose concentrations of 5 mM, 84 mM, 138 mM, and 236 mM. Additionally, N-acetylcysteine (NAC) was used as an antioxidant to clarify the mechanism of high-dialysate-glucose-induced apoptosis. Exposing HPMCs to high-dialysate glucose resulted in substantial apoptosis with cytochrome c release, followed by caspase activation and poly(ADP-ribose) polymerase cleavage. High-dialysate glucose induced excessive reactive oxygen species production and lipid peroxidation as well as oxidative damage to DNA. Mitochondrial fragmentation, multiple mitochondrial DNA deletions, and dissipation of the mitochondrial membrane potential were also observed. The mitochondrial dysfunction and cell death were suppressed using NAC. These results indicated that mitochondrial dysfunction is one of the main causes of high-dialysate-glucose-induced HPMC apoptosis.

Ischemic Preconditioning Is Capable of Inducing Mitochondrial Tolerance in the Rat Brain

2002 ◽  
Vol 97 (4) ◽  
pp. 896-901 ◽  
Author(s):  
Ren-Zhi Zhan ◽  
Hideyoshi Fujihara ◽  
Hiroshi Baba ◽  
Tomohiro Yamakura ◽  
Koki Shimoji
Keyword(s):  
Cerebral Ischemia ◽  
Cytochrome C ◽  
Mitochondrial Dysfunction ◽  
Ischemic Preconditioning ◽  
Neuronal Death ◽  
Brain Mitochondria ◽  
Sham Operation ◽  
Cytochrome C Release ◽  
Hippocampal Ca1 ◽  
Ischemic Episode

Background Preconditioning to ischemia is a phenomenon whereby a brief episode of sublethal ischemia and other nonlethal stressors produce protection against a subsequent detrimental ischemic insult. As mitochondrial dysfunction is related to necrotic and apoptotic neuronal death after cerebral ischemia, the authors examined if ischemic preconditioning is capable of inducing mitochondrial tolerance. Methods Forebrain ischemia was induced by bilateral common carotid artery occlusion with simultaneous hypotension for 8 min in Wistar rats (275-300 g). A 3-min ischemic episode performed 48 h before the 8-min ischemia was used for preconditioning. The extents of hippocampal CA1 neuronal damage were evaluated 7 days after reperfusion by neuro-specific nuclear protein immunostaining. Brain mitochondria were isolated 48 h after animals were subjected to the sham operation or the 3-min conditioning ischemia. Loss of cytochrome c from mitochondria after cerebral ischemia in vivo and after exposure of brain mitochondria to calcium in vitro was used as an indication of mitochondrial dysfunction. Results Results showed that ischemic preconditioning induced by a 3-min ischemic episode dramatically reduced the loss of hippocampal CA1 neurons resulting from a subsequent 8-min ischemia 7 days after reperfusion, and this protection was associated with a preservation of mitochondrial cytochrome c as examined after early reperfusion. Exposure of isolated brain mitochondria to calcium produced a dose-dependent increase in cytochrome c release either at 30 degrees C or at 37 degrees C. Compared with those animals receiving only sham operation, cytochrome c release caused by 100 microm calcium was significantly reduced in conditioned animals. Conclusion Regarding the importance of mitochondrial dysfunction in mediating ischemic neuronal death, the above results indicate that mitochondria may serve as end-effecting organelles to ischemic preconditioning.

scholarly journals Geniposide Prevents Hypoxia/Reoxygenation-Induced Apoptosis in H9c2 Cells: Improvement of Mitochondrial Dysfunction and Activation of GLP-1R and the PI3K/AKT Signaling Pathway

2016 ◽  
Vol 39 (1) ◽  
pp. 407-421 ◽  
Author(s):  
You-Qin Jiang ◽  
Guang-lei Chang ◽  
Ying Wang ◽  
Dong-Ying Zhang ◽  
Li Cao ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Cell Viability ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Membrane ◽  
Caspase 3 ◽  
Akt Signaling ◽  
Mitochondrial Morphology ◽  
Mitochondrial Calcium ◽  
H9c2 Cells ◽  
Akt Signaling Pathway

Background/Aims: Myocardial ischemia/reperfusion injury is a major cause of morbidity and mortality associated with coronary heart disease. Many studies have demonstrated that natural products are promising chemotherapeutic drugs counteracting the loss of cardiomyocytes. Thus, the purpose of the present study was to investigate the effects of geniposide, a traditional Chinese herb extract from Gardenia jasminoides J. Ellis, on cardiomyocyte apoptosis induced by hypoxia/reoxygenation (H/R) in H9c2 cells, and their underlying mechanisms. Methods: Cell viability and apoptosis ratio were assessed using the cell counting kit-8 assay and Annexin V/propidium iodide (PI) staining. The concentrations of lactate dehydrogenase (LDH), intracellular total superoxide dismutase (T-SOD), and malondialdehyde (MDA) were detected by microplate reader. The production of reactive oxygen species/reactive nitrogen species (ROS/RNS), the level of mitochondrial calcium, and mitochondrial membrane potential depolarization were measured by confocal laser scanning microscopy. Mitochondrial morphology was visualized using transmission electron microscopy. The expressions of Bcl-2 mRNA and Caspase-3 mRNA were measured by reverse transcription-polymerase chain reaction (RT-PCR). The protein levels of cleaved caspase-3, Bcl-2, Bax, AKT, p-AKTserine473, cytochrome-c were detected by western bloting. Results: Geniposide pretreatment increased cell viability, decreased LDH levels in the supernatant, and inhibited cardiomyocyte apoptosis caused by H/R. Furthermore, geniposide reversed mitochondrial dysfunction by decreasing oxidative stress products (ROS/RNS and MDA), increasing anti-oxidative enzyme (T-SOD) level, improving mitochondrial morphology, attenuating mitochondrial calcium overload and blunting depolarization of mitochondrial membrane. Moreover, geniposide pretreatment increased Bcl-2 level and decreased Bax level, thus enhancing the Bcl-2/Bax ratio. Consistent with the above result, Bcl-2 mRNA expression was upregulated and caspase-3 mRNA expression was downregulated by geniposide. In addition, geniposide decreased the protein expression of cleaved caspase-3 and cytochrome-c and increased the level p-AKTserine473. The protective effects of geniposide were partially reversed by glucagon-like pepitide-1 receptor antagonist exendin-(9-39) and the phosphatidylinositol 3 kinase (PI3K) inhibitor LY294002. Conclusions: Our results suggest that geniposide pretreatment inhibits H/R-induced myocardial apoptosis by reversing mitochondrial dysfunction, an effect in part due to activation of GLP-1R and PI3K/AKT signaling pathway.

scholarly journals Transcriptional mechanisms and protein kinase signaling mediate organic dust induction of IL-8 expression in lung epithelial and THP-1 cells

2015 ◽  
Vol 308 (1) ◽  
pp. L11-L21 ◽  
Author(s):  
Koteswara R. Gottipati ◽  
Shiva Kumar Bandari ◽  
Matthew W. Nonnenmann ◽  
Jeffrey L. Levin ◽  
Gregory P. Dooley ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Inflammatory Responses ◽  
Dust Exposure ◽  
Kinase Signaling ◽  
Organic Dust ◽  
Chronic Lung Diseases ◽  
Lung Epithelial ◽  
Poultry Dust ◽  
Protein Kinase Signaling ◽  
Dust Extract

Exposure to the agricultural work environment is a risk factor for the development of respiratory symptoms and chronic lung diseases. Inflammation is an important contributor to the pathogenesis of tissue injury and disease. Cellular and molecular mechanisms mediating lung inflammatory responses to agricultural dust are not yet fully understood. We studied the effects of poultry dust extract on molecular regulation of interleukin-8 (IL-8), a proinflammatory cytokine, in A549 and Beas2B lung epithelial and THP-1 monocytic cells. Our findings indicate that poultry dust extract potently induces IL-8 levels by increasing IL-8 gene transcription without altering IL-8 mRNA stability. Increase in IL-8 promoter activity was due to enhanced binding of activator protein 1 and NF-κB. IL-8 induction was associated with protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) activation and inhibited by PKC and MAPK inhibitors. IL-8 increase was not inhibited by polymyxin B or l-nitroarginine methyl ester, indicating lack of involvement of lipopolysaccharide and nitric oxide in the induction. Lung epithelial and THP-1 cells share common mechanisms for induction of IL-8 levels. Our findings identify key roles for transcriptional mechanisms and protein kinase signaling pathways for IL-8 induction and provide insights into the mechanisms regulating lung inflammatory responses to organic dust exposure.

scholarly journals Organic dust exposure induces stress response and mitochondrial dysfunction in monocytic cells

2021 ◽  
Author(s):  
Sanjana Mahadev Bhat ◽  
Denusha Shrestha ◽  
Nyzil Massey ◽  
Locke A. Karriker ◽  
Anumantha G. Kanthasamy ◽  
...  
Keyword(s):  
Stress Response ◽  
Mitochondrial Dysfunction ◽  
Dust Exposure ◽  
Organic Dust ◽  
Monocytic Cells

scholarly journals Melatonin Protects Tobacco Suspension Cells against Pb-Induced Mitochondrial Dysfunction

2021 ◽  
Vol 22 (24) ◽  
pp. 13368
Author(s):  
Agnieszka Kobylińska ◽  
Małgorzata Maria Posmyk
Keyword(s):  
Cytochrome C ◽  
Mitochondrial Dysfunction ◽  
Plant Tolerance ◽  
Suspension Cells ◽  
Cytochrome C Release ◽  
Bright Yellow ◽  
Nicotiana Tabacum L ◽  
Tobacco Suspension Cells ◽  
Defence Strategies

Recent studies have shown that melatonin is an important molecule in plant physiology. It seems that the most important is that melatonin effectively eliminates oxidative stress (direct and indirect antioxidant) and switches on different defence strategies (preventive and interventive actions) during environmental stresses. In the presented report, exogenous melatonin potential to protect Nicotiana tabacum L. line Bright Yellow 2 (BY-2) exposed to lead against death was examined. Analyses of cell proliferation and viability, the level of intracellular calcium, changes in mitochondrial membrane potential (ΔΨm) as well as possible translocation of cytochrome c from mitochondria to cytosol and subsequent caspase-like proteolytic activity were conducted. Our results indicate that pretreatment BY-2 with melatonin protected tobacco cells against mitochondrial dysfunction and caspase-like activation caused by lead. The findings suggest the possible role of this indoleamine in the molecular mechanism of mitochondria, safeguarding against potential collapse and cytochrome c release. Thus, it seems that applied melatonin acted as an effective factor, promoting survival and increasing plant tolerance to lead.

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