LPS Induces Hypoxia-Inducible Factor 1 Activation in Macrophage-Differentiated Cells in a Reactive Oxygen Species–Dependent Manner

2008 ◽  
Vol 10 (5) ◽  
pp. 983-996 ◽  
Author(s):  
Kenichiro Nishi ◽  
Tomoyuki Oda ◽  
Satoshi Takabuchi ◽  
Seiko Oda ◽  
Kazuhiko Fukuda ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Hypoxia Inducible Factor ◽  
Reactive Oxygen ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Hypoxia Inducible Factor 1 ◽  
Differentiated Cells

scholarly journals Reactive Oxygen Species and Nrf2: Functional and Transcriptional Regulators of Hematopoiesis

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Linping Hu ◽  
Yawen Zhang ◽  
Weimin Miao ◽  
Tao Cheng
Keyword(s):  
Reactive Oxygen Species ◽  
Oxygen Sensor ◽  
Hypoxia Inducible Factor ◽  
Reactive Oxygen ◽  
Ambient Air ◽  
Oxygen Species ◽  
Human Cord Blood ◽  
Hematopoietic Stem ◽  
Hypoxia Inducible Factor 1 ◽  
Cellular Oxygen

Hematopoietic stem cells (HSCs) are characterized by self-renewal and multilineage differentiation potentials. Although they play a central role in hematopoietic homeostasis and bone marrow (BM) transplantation, they are affected by multiple environmental factors in the BM. Here, we review the effects of reactive oxygen species (ROS) and Nrf2 on HSC function and BM transplantation. HSCs reside in the hypoxic microenvironment of BM, and ROS play an important role in HSPC regulation. Recently, an extraphysiologic oxygen shock/stress phenomenon was identified in human cord blood HSCs collected under ambient air conditions. Moreover, Nrf2 has been recently recognized as a master transcriptional factor that regulates multiple antioxidant enzymes. Since several years, the role of Nrf2 in hematopoiesis has been extensively studied, which has functional similarities of cellular oxygen sensor hypoxia-inducible factor-1 as transcriptional factors. Increasing evidence has revealed that abnormally elevated ROS production due to factors such as genetic defects, aging, and ionizing radiation unexceptionally resulted in lethal impairment of HSC function and hematopoiesis. Both experimental and clinical studies have identified elevated ROS levels as a major culprit of ineffective BM transplantation. Lastly, we discuss the possibility of using small molecule antioxidants, such as N-acetyl cysteine, resveratrol, and curcumin, to augment HSC function and improve the therapeutic efficacy of BM transplantation. Further research on the function of ROS levels and improving the efficacy of BM transplantation may have a great potential for broad clinical applications of HSCs.

scholarly journals Hypoxia-inducible Factor-1 Activation in Nonhypoxic Conditions: The Essential Role of Mitochondrial-derived Reactive Oxygen Species

2010 ◽  
Vol 21 (18) ◽  
pp. 3247-3257 ◽  
Author(s):  
David A. Patten ◽  
Véronique N. Lafleur ◽  
Geneviève A. Robitaille ◽  
Denise A. Chan ◽  
Amato J. Giaccia ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Hypoxia Inducible Factor ◽  
Reactive Oxygen ◽  
Protein Stabilization ◽  
Complex Iii ◽  
Oxygen Species ◽  
Ang Ii ◽  
Hypoxia Inducible Factor 1

Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor for responses to low oxygen. Different nonhypoxic stimuli, including hormones and growth factors, are also important HIF-1 activators in the vasculature. Angiotensin II (Ang II), the main effecter hormone in the renin-angiotensin system, is a potent HIF-1 activator in vascular smooth muscle cells (VSMCs). HIF-1 activation by Ang II involves intricate mechanisms of HIF-1α transcription, translation, and protein stabilization. Additionally, the generation of reactive oxygen species (ROS) is essential for HIF-1 activation during Ang II treatment. However, the role of the different VSMC ROS generators in HIF-1 activation by Ang II remains unclear. This work aims at elucidating this question. Surprisingly, repression of NADPH oxidase-generated ROS, using Vas2870, a specific inhibitor or a p22phox siRNA had no significant effect on HIF-1 accumulation by Ang II. In contrast, repression of mitochondrial-generated ROS, by complex III inhibition, by Rieske Fe-S protein siRNA, or by the mitochondrial-targeted antioxidant SkQ1, strikingly blocked HIF-1 accumulation. Furthermore, inhibition of mitochondrial-generated ROS abolished HIF-1α protein stability, HIF-1–dependent transcription and VSMC migration by Ang II. A large number of studies implicate NADPH oxidase–generated ROS in Ang II–mediated signaling pathways in VSMCs. However, our work points to mitochondrial-generated ROS as essential intermediates for HIF-1 activation in nonhypoxic conditions.

scholarly journals HIF1A-dependent increase in endothelin 2 levels in granulosa cells: role of hypoxia, LH/cAMP, and reactive oxygen species

Reproduction ◽  
2015 ◽  
Vol 149 (1) ◽  
pp. 11-20 ◽  
Author(s):  
Ronit Yalu ◽  
Adepeju Esther Oyesiji ◽  
Iris Eisenberg ◽  
Tal Imbar ◽  
Rina Meidan
Keyword(s):  
Reactive Oxygen Species ◽  
Mrna Expression ◽  
Granulosa Cells ◽  
Time Window ◽  
Hypoxia Inducible Factor ◽  
Reactive Oxygen ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Protein Levels ◽  
Concomitant Reduction

Hypoxia-inducible factor 1 alpha (HIF1A) and endothelin 2 (EDN2) are transiently expressed during the same time window in the developing corpus luteum (CL). In this study, we sought to investigate the involvement of LH/cAMP, reactive oxygen species (ROS), and a hypoxia-mimetic compound (CoCl2) on HIF1A expression and how it affected EDN2 levels, using transformed human granulosa cells (thGCs) and primary bovine granulosa cells (GCs). CoCl2 elevated HIF1A protein levels in thGCs in a dose-dependent manner. Forskolin alone had no significant effect; however, forskolin and CoCl2 together further induced HIF1A protein and EDN2 mRNA expression in thGCs. Similarly, in primary GCs, LH with CoCl2 synergistically augmented HIF1A protein levels, which resulted in higher expression of EDN2 and another well-known hypoxia-inducible gene, VEGF (VEGFA). Importantly, LH alone elevated HIF1A mRNA but not its protein. The successful knockdown of HIF1A in thGCs using siRNA abolished hypoxia-induced EDN2 and also the additive effect of forskolin and CoCl2. We then examined the roles of ROS in thGCs: hydrogen peroxide (20 and 50 μM) elevated HIF1A protein as well as the expression of EDN2, implying that induction of HIF1A protein levels is sufficient to stimulate the expression of EDN2 (and VEGF) in normoxia. A broad-range ROS scavenger, butylated hydroxyanisole, inhibited CoCl2-induced HIF1A protein with a concomitant reduction in the mRNA expression of EDN2 and VEGF in thGCs. The results obtained in this study suggest that HIF1A, induced by various stimuli, is an essential mediator of EDN2 mRNA expression. The results may also explain the rise in the levels of HIF1A-dependent genes (EDN2 and VEGF) in the developing CL.

scholarly journals Cigarette Smoke Extract Activates Hypoxia-Inducible Factors in a Reactive Oxygen Species-Dependent Manner in Stroma Cells from Human Endometrium

Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 48
Author(s):  
Naoko Kida ◽  
Yoshiyuki Matsuo ◽  
Yoshiko Hashimoto ◽  
Kenichiro Nishi ◽  
Tomoko Tsuzuki-Nakao ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Stromal Cells ◽  
Hypoxia Inducible Factor ◽  
Reactive Oxygen ◽  
Protein Stabilization ◽  
Human Endometrium ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Endometrial Stromal Cells ◽  
Hypoxic Conditions

Cigarette smoking (CS) is a major contributing factor in the development of a large number of fatal and debilitating disorders, including degenerative diseases and cancers. Smoking and passive smoking also affect the establishment and maintenance of pregnancy. However, to the best of our knowledge, the effects of smoking on the human endometrium remain poorly understood. In this study, we investigated the regulatory mechanism underlying CS-induced hypoxia-inducible factor (HIF)-1α activation using primary human endometrial stromal cells and an immortalized cell line (KC02-44D). We found that the CS extract (CSE) increased reactive oxygen species levels and stimulated HIF-1α protein stabilization in endometrial stromal cells, and that CS-induced HIF-1α-dependent gene expression under non-hypoxic conditions in a concentration- and time-dependent manner. Additionally, we revealed the upregulated expression of a hypoxia-induced gene set following the CSE treatment, even under normoxic conditions. These results indicated that HIF-1α might play an important role in CS-exposure-induced cellular stress, inflammation, and endometrial remodeling.

scholarly journals Repression of Hypoxia-Inducible Factor-1 Contributes to Increased Mitochondrial Reactive Oxygen Species Production in Diabetes

2021 ◽  
Author(s):  
Xiaowei Zheng ◽  
Sampath Narayanan ◽  
Cheng Xu ◽  
Sofie Eliasson Angelstig ◽  
Jacob Grünler ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Hypoxia Inducible Factor ◽  
Reactive Oxygen ◽  
Pyruvate Dehydrogenase Kinase ◽  
Oxygen Species ◽  
Mitochondrial Reactive Oxygen Species ◽  
Glucose Levels ◽  
Hypoxia Inducible Factor 1 ◽  
Mitochondrial Ros ◽  
Functional Consequences

Background: Excessive production of mitochondrial reactive oxygen species (ROS) is a central mechanism for the development of diabetes complications. Recently, hypoxia has been identified to play an additional pathogenic role in diabetes. In this study, we hypothesized that ROS overproduction was secondary to the impaired responses to hypoxia due to the inhibition of hypoxia-inducible factor-1 (HIF-1) by hyperglycemia. Methods: The dynamic of ROS levels was analysed in the blood of healthy subjects and individuals with type 1 diabetes after exposure to hypoxia (ClinicalTrials.gov registration no. NCT02629406). The relation between HIF-1, glucose levels, ROS production and its functional consequences were analyzed in renal mIMCD-3 cells and in kidneys of mouse models of diabetes. Results: Exposure to hypoxia increased circulating ROS in subjects with diabetes, but not in subjects without diabetes. High glucose concentrations repressed HIF-1 both in hypoxic cells and in kidneys of animals with diabetes, through a HIF prolyl-hydroxylase (PHD) - dependent mechanism. The impaired HIF-1 signaling contributed to excess production of mitochondrial ROS through increased mitochondrial respiration that was mediated by Pyruvate dehydrogenase kinase 1 (PDK1) and was followed by functional consequences. The restoration of HIF-1 function attenuated ROS overproduction despite persistent hyperglycemia, and conferred protection against apoptosis and renal injury in diabetes. Conclusions: We conclude that the repression of HIF-1 plays a central role in mitochondrial ROS overproduction in diabetes and is a potential therapeutic target for diabetic complications. These findings are highly significant and timely since the first PHD inhibitor that can activate HIF-1 has been newly approved for clinical use.

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