Mitochondrial dysfunction and HIF1α stabilization in inflammation

Garedew, Assegid; Moncada, Salvador

doi:10.1242/jcs.034660

Cited by 27 publications

(11 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, we estimated the amount of HIF-1α in the cytoplasm and the amount translocated into the nucleus of HUVECs following CNPI treatment. Figure 6A and B present the amount of HIF-1α in cytoplasmic and nuclear fraction in control, CNPI and CoCl 2 (Positive control) treated cells [30]. A higher amount of HIF-1α in cytoplasmic fraction was observed in cells treated with CNPI (both 30 min and 2 h treatment) (Figure 6A).…”

Section: Resultsmentioning

confidence: 99%

The induction of angiogenesis by cerium oxide nanoparticles through the modulation of oxygen in intracellular environments

et al. 2012

View full text Add to dashboard Cite

Angiogenesis is the formation of new blood vessels from existing blood vessels and is critical for many physiological and pathophysiological processes. In this study we have shown the unique property of cerium oxide nanoparticle (CNPs) to induce angiogenesis, observed using both in vitro and in vivo model systems. In particular, CNPs trigger angiogenesis by modulating the intracellular oxygen environment and stabilizing hypoxia inducing factor 1α endogenously. Furthermore, correlations between angiogenesis induction and CNPs physicochemical properties including: surface Ce3+/Ce4+ ratio, surface charge, size, and shape were also explored. High surface area and increased Ce3+/Ce4+ ratio make CNPs more catalytically active towards regulating intracellular oxygen, which in turn led to more robust induction of angiogenesis. Atomistic simulation was also used, in partnership with in vitro and in vivo experimentation, to reveal that the surface reactivity of CNPs and facile oxygen transport promotes pro-angiogenesis.

show abstract

Section: Resultsmentioning

confidence: 99%

The induction of angiogenesis by cerium oxide nanoparticles through the modulation of oxygen in intracellular environments

et al. 2012

View full text Add to dashboard Cite

show abstract

“…As ROS and iNOS expressions increase at day 3, nitrosative stress and protein thiol S-nitrosylation (SNO) as well as tyrosine nitration activities will be enhanced [58–60]. Initially, SNO modification of pro-apoptotic caspase-3 prevents its release from mitochondria [60]; however continued ROS/RNS will damage proteins, nucleic acids, and organelles including ER and mitochondria.…”

Section: Discussionmentioning

confidence: 99%

“…Sustained ROS/RNS generation and activation of autophagy/mitophagy will eventually trigger an apoptotic signal and premature cell death due to excessive removal of essential organelles and proteins in the cell while damaged mitochondria leaks electrons [57, 58]. Mitochondrial oxidative/nitrosative stress causes ER stress, which in turn induces mitochondrial damage thus generating a vicious cycle of organelle damage and tissue injury [41].…”

Section: Discussionmentioning

confidence: 99%

TXNIP Links Innate Host Defense Mechanisms to Oxidative Stress and Inflammation in Retinal Muller Glia under Chronic Hyperglycemia: Implications for Diabetic Retinopathy

Devi

Lee

Hüttemann

et al. 2012

Experimental Diabetes Research

175

213

View full text Add to dashboard Cite

Thioredoxin Interacting Protein (TXNIP) mediates retinal inflammation, gliosis, and apoptosis in experimental diabetes. Here, we investigate the temporal response of Muller glia to high glucose (HG) and TXNIP expression using a rat Muller cell line (rMC1) in culture. We examined if HG-induced TXNIP expression evokes host defense mechanisms in rMC1 in response to metabolic abnormalities. HG causes sustained up-regulation of TXNIP (2 h to 5 days), ROS generation, ATP depletion, ER stress, and inflammation. Various cellular defense mechanisms are activated by HG: (i) NLRP3 inflammasome, (ii) ER stress response (sXBP1), (iii) hypoxic-like HIF-1α induction, (iv) autophagy/mitophagy, and (v) apoptosis. We also found in vivo that streptozocin-induced diabetic rats have higher retinal TXNIP and innate immune response gene expression than normal rats. Knock down of TXNIP by intravitreal siRNA reduces inflammation (IL-1β) and gliosis (GFAP) in the diabetic retina. TXNIP ablation in vitro prevents ROS generation, restores ATP level and autophagic LC3B induction in rMC1. Thus, our results show that HG sustains TXNIP up-regulation in Muller glia and evokes a program of cellular defense/survival mechanisms that ultimately lead to oxidative stress, ER stress/inflammation, autophagy and apoptosis. TXNIP is a potential target to ameliorate blinding ocular complications of diabetic retinopathy.

show abstract

“…For example NO-mediated mitochondrial inhibition in dendritic cells leads to a switch from oxidative to glycolic metabolism similar to the Warburg effect that is observed in hypoxic cancer cells [216]. Other studies indicate that stabilization of HIF-1α by NO leads to an increase in glycolytic pathways [217] as well as activation of AMPK [218]. These metabolic shifts can have significant downstream effects, specifically on epigenetic regulatory mechanisms [219].…”

Section: Rns-derived Modificationsmentioning

confidence: 99%

Signaling and stress: The redox landscape in NOS2 biology

Thomas

Heinecke

Ridnour

et al. 2015

Free Radical Biology and Medicine

126

109

View full text Add to dashboard Cite

Nitric oxide (NO) has a highly diverse range of biological functions from physiological signaling and maintenance of homeostasis to serving as an effector molecule in the immune system. Many of the dichotomous effects of NO and derivative reactive nitrogen species (RNS) can be explained by invoking precise interactions with different targets as a result of concentration and temporal constraints. Endogenous concentrations of NO span five orders of magnitude, with levels near the high picomolar range typically occurring in short bursts as compared to sustained production of low micromolar levels of NO during immune response. This article provides an overview of the redox landscape as it relates to increasing NO concentrations, which incrementally govern physiological signaling, nitrosative signaling and nitrosative stress-related signaling. Physiological signaling by NO primarily occurs upon interaction with the heme protein soluble guanylyl cyclase. As NO concentrations rise, interactions with nonheme iron complexes as well as indirect modification of thiols can stimulate additional signaling processes. At the highest levels of NO, production of a broader range of RNS, which subsequently interact with more diverse targets, can lead to chemical stress. However, even under such conditions, there is evidence that stress-related signaling mechanisms are triggered to protect cells or even resolve the stress. This review therefore also addresses the fundamental reactions and kinetics that initiate signaling through NO-dependent pathways, including the chemistry of RNS and their molecular targets.

show abstract

Mitochondrial dysfunction and HIF1α stabilization in inflammation

Cited by 27 publications

References 42 publications

The induction of angiogenesis by cerium oxide nanoparticles through the modulation of oxygen in intracellular environments

The induction of angiogenesis by cerium oxide nanoparticles through the modulation of oxygen in intracellular environments

TXNIP Links Innate Host Defense Mechanisms to Oxidative Stress and Inflammation in Retinal Muller Glia under Chronic Hyperglycemia: Implications for Diabetic Retinopathy

Signaling and stress: The redox landscape in NOS2 biology

Contact Info

Product

Resources

About