Journal ArticleDOI
Cellular and molecular mechanisms in the hypoxic tissue: role of HIF-1 and ROS.
Andrea B. Zepeda,Adalberto Pessoa,Rodrigo L. Castillo,Carolina A. Figueroa,Victor M Pulgar,Victor M Pulgar,Jorge G. Farías +6 more
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TLDR
New developments in HIF‐mediated O2 sensing mechanisms and their interactions with reactive oxygen species–generating pathways in normal and abnormal physiology are summarized.Abstract:
Reactive oxygen species such as superoxide anion radicals (O2 (-) ) and hydrogen peroxide (H2 O2 ) have for long time been recognized as undesirable by-products of the oxidative mitochondrial generation of adenosine triphosphate (ATP). Recently, these highly reactive species have been associated to important signaling pathways in diverse physiological conditions such as those activated in hypoxic microenvironments. The molecular response to hypoxia requires fast-acting mechanisms acting within a wide range of partial pressures of oxygen (O2 ). Intracellular O2 sensing is an evolutionary preserved feature, and the best characterized molecular responses to hypoxia are mediated through transcriptional activation. The transcription factor, hypoxia-inducible factor 1 (HIF-1), is a critical mediator of these adaptive responses, and its activation by hypoxia involves O2 -dependent posttranslational modifications and nuclear translocation. Through the induction of the expression of its target genes, HIF-1 coordinately regulates tissue O2 supply and energetic metabolism. Other transcription factors such as nuclear factor κB are also redox sensitive and are activated in pro-oxidant and hypoxic conditions. The purpose of this review is to summarize new developments in HIF-mediated O2 sensing mechanisms and their interactions with reactive oxygen species-generating pathways in normal and abnormal physiology.read more
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Oxidative stress and free radicals in COPD – implications and relevance for treatment
TL;DR: The general relevance of free radicals for the development and progression of both COPD and pulmonary emphysema is focused on as well as novel perspectives on therapeutic options.
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The Warburg effect: evolving interpretations of an established concept.
TL;DR: The new finding that a significant amount of glycolytic intermediates is diverted to the pentose phosphate pathway (PPP) for production of NADPH has profound implications in how cancer cells use the Warburg effect to cope with reactive oxygen species (ROS) generation and oxidative stress, opening the door for anticancer interventions taking advantage of this.
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Signalling pathways involved in hypoxia-induced renal fibrosis.
TL;DR: This review will focus on the signalling pathways involved in hypoxia‐induced pathogenesis of interstitial fibrosis, including pathways mediated by HIF, TGF‐β, Notch, PKC/ERK, PI3K/Akt, NF‐κB, Ang II/ROS and microRNAs.
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LncRNA EPB41L4A-AS1 regulates glycolysis and glutaminolysis by mediating nucleolar translocation of HDAC2
Meijian Liao,Weijie Liao,Naihan Xu,Bing Li,Fuhai Liu,Shikuan Zhang,Yanzhi Wang,Songmao Wang,Yuanchang Zhu,Deheng Chen,Weidong Xie,Yuyang Jiang,Liu Cao,Burton B. Yang,Yaou Zhang +14 more
TL;DR: EPB41L4A-AS1 functions as a repressor of the Warburg effect and plays important roles in metabolic reprogramming of cancer.
Journal ArticleDOI
Pin1 cysteine-113 oxidation inhibits its catalytic activity and cellular function in Alzheimer’s disease
Chun Hau Chen,Wenzong Li,Rukhsana Sultana,Mi Hyeon You,Asami Kondo,Koorosh Shahpasand,Byeong Mo Kim,Man Li Luo,Morris Nechama,Yu-Min Lin,Yandan Yao,Tae Ho Lee,Xiao Zhen Zhou,Aaron M. Swomley,D. Allan Butterfield,Yan Zhang,Kun Ping Lu,Kun Ping Lu +17 more
TL;DR: A novel Pin1 oxidation site is identified to be the critical catalytic residue Cys113, which provides a novel oxidative regulation mechanism for inhibiting Pin1 activity in AD and suggests that preventing Pin1 oxidization might help to reduce the risk of AD.
References
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Journal ArticleDOI
NF-κB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1α
Jordi Rius,Monica Guma,Christian Schachtrup,Katerina Akassoglou,Annelies S. Zinkernagel,Victor Nizet,Randall S. Johnson,Gabriel G. Haddad,Michael Karin +8 more
TL;DR: It is shown, with the use of mice lacking IKK-β in different cell types, that NF-κB is a critical transcriptional activator of HIF-1α and that basal NF-σB activity is required for Hif-1 α protein accumulation under hypoxia in cultured cells and in the liver and brain of hypoxic animals.
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Regulation of Hypoxia-Inducible Factor 1α Expression and Function by the Mammalian Target of Rapamycin
Christine C. Hudson,Mei Liu,Gary G. Chiang,Diane M. Otterness,Dawn C. Loomis,Fiona Kaper,Amato J. Giaccia,Robert T. Abraham +7 more
TL;DR: These studies position mTOR as an upstream activator of HIF-1 function in cancer cells and suggest that the antitumor activity of rapamycin is mediated, in part, through the inhibition of cellular responses to hypoxic stress.
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Hypoxia and metabolism. Hypoxia, DNA repair and genetic instability.
TL;DR: Acute and chronic hypoxia might lead to different biology within the tumour and this might have a direct effect on the design of new therapies for the treatment of hypoxic tumours.
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Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response
TL;DR: A constant theme emerges: inhibition of HIF1 activity will have therapeutic benefit, both spatially and temporally, in the hypoxic environment of tumours.
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Radiation activates HIF-1 to regulate vascular radiosensitivity in tumors: role of reoxygenation, free radicals, and stress granules
TL;DR: Novel pathways contributing significantly to the understanding of HIF-1 regulation which may be major determinants of tumor radiosensitivity, potentially having high clinical relevance are described.