scholarly journals How decreasing oxygenase activity helps cells cope with hypoxia

2016 ◽  
Vol 38 (5) ◽  
pp. 26-29 ◽  
Author(s):  
Emily Flashman

The ability of our bodies to adapt to reduced oxygen availability (hypoxia) by increasing red blood cell formation was recognized in the 19th century, but almost 200 years passed before the molecular mechanism underlying this hypoxic response was revealed. In animals, hypoxia tolerance is enabled by turning on a plethora of genes, all under the control of the hypoxia inducible transcription factor protein, HIF. Crucially, levels of HIF are controlled by a set of enzymes, whose activity is exquisitely sensitive to oxygen availability. A low-oxygen response system is arguably more important for plants which, as sessile organisms, cannot employ behavioural responses to hypoxia, and recent findings reveal a distinct yet analogous mechanism. It seems that in plants as well as in animals, oxygen-dependent enzymes are the linchpins connecting oxygen availability with the cellular response to hypoxia.

2014 ◽  
Vol 92 (7) ◽  
pp. 569-589 ◽  
Author(s):  
Matthew E. Pamenter

Decreased oxygen availability impairs cellular energy production and, without a coordinated and matched decrease in energy consumption, cellular and whole organism death rapidly ensues. Of particular interest are mechanisms that protect brain from low oxygen injury, as this organ is not only the most sensitive to hypoxia, but must also remain active and functional during low oxygen stress. As a result of natural selective pressures, some species have evolved molecular and physiological mechanisms to tolerate prolonged hypoxia with no apparent detriment. Among these mechanisms are a handful of responses that are essential for hypoxia tolerance, including (i) sensors that detect changes in oxygen availability and initiate protective responses; (ii) mechanisms of energy conservation; (iii) maintenance of basic brain function; and (iv) avoidance of catastrophic cell death cascades. As the study of hypoxia-tolerant brain progresses, it is becoming increasingly apparent that mitochondria play a central role in regulating all of these critical mechanisms. Furthermore, modulation of mitochondrial function to mimic endogenous neuroprotective mechanisms found in hypoxia-tolerant species confers protection against otherwise lethal hypoxic stresses in hypoxia-intolerant organs and organisms. Therefore, lessons gleaned from the investigation of endogenous mechanisms of hypoxia tolerance in hypoxia-tolerant organisms may provide insight into clinical pathologies related to low oxygen stress.


1995 ◽  
Vol 9 (5) ◽  
pp. 1274-1288 ◽  
Author(s):  
LAUREN J. CHAPMAN ◽  
LESLIE S. KAUFMAN ◽  
COLIN A. CHAPMAN ◽  
F. ELLIS MCKENZIE

Author(s):  
Till S Harter ◽  
Alexander M Clifford ◽  
Martin Tresguerres

White seabass (Atractoscion nobilis) increasingly experience periods of low oxygen (O2; hypoxia) and high carbon dioxide (CO2, hypercapnia) due to climate change and eutrophication of the coastal waters of California. Hemoglobin (Hb) is the principal O2 carrier in the blood and in many teleost fishes Hb-O2 binding is compromised at low pH; however, the red blood cells (RBC) of some species regulate intracellular pH with adrenergically-stimulated sodium-proton-exchangers (β-NHE). We hypothesized that RBC β-NHEs in white seabass are an important mechanism that can protect the blood O2-carrying capacity during hypoxia and hypercapnia. We determined the O2-binding characteristics of white seabass blood, the cellular and sub-cellular response of RBCs to adrenergic stimulation, and quantified the protective effect of β-NHE activity on Hb-O2 saturation. White seabass had typical teleost Hb characteristics, with a moderate O2 affinity (PO2 at half-saturation; P50 2.9 kPa) that was highly pH-sensitive (Bohr coefficient -0.92; Root effect 52%). Novel findings from super-resolution microscopy revealed β-NHE protein in vesicle-like structures and its translocation into the membrane after adrenergic stimulation. Microscopy data were corroborated by molecular and phylogenetic results, and a functional characterization of β-NHE activity. The activation of RBC β-NHEs increased Hb-O2 saturation by ~8% in normoxic hypercapnia, and by up to ~20% in hypoxic normocapnia. Our results provide novel insight into the cellular mechanism of adrenergic RBC stimulation within an ecologically relevant context. β-NHE activity in white seabass has great potential to protect arterial O2 transport during hypoxia and hypercapnia but is less effective during combinations of these stressors.


2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Kayla L Gilmore ◽  
Zoe A Doubleday ◽  
Bronwyn M Gillanders

Lay summary It is poorly understood whether fish can acclimate to prolonged low-oxygen conditions (or hypoxia). Our study shows that prior long-term exposure to low-oxygen conditions improves tolerance to low-oxygen in a freshwater fish. The results of our study aid our understanding of long-term responses of freshwater fish to low-oxygen to hypoxic events.


2014 ◽  
Vol 95 (3) ◽  
pp. 490-496 ◽  
Author(s):  
Silvia Fornaciari ◽  
Francesco Milano ◽  
Francesca Mussi ◽  
Laura Pinto-Sanchez ◽  
Luca Forti ◽  
...  

2018 ◽  
Vol 102 (13) ◽  
pp. 5785-5785
Author(s):  
Bruno Labate Vale da Costa ◽  
Thiago Olitta Basso ◽  
Vijayendran Raghavendran ◽  
Andreas Karoly Gombert

Author(s):  
Shawn C. Oppegard ◽  
David T. Eddington

Oxygen is a key modulator of many cellular pathways and plays an important role in a number of cellular behaviors. The hypoxic inducible factor 1α (HIF-1α) is often considered the master regulator of the cellular response to oxygen tension (1). HIF-1α is a transcription factor involved in angiogenesis, glucose transport and glycolysis, apoptosis, migration, and differentiation, among many other functions (2). Unfortunately devices permitting in vitro oxygen modulation fail to meet the needs of biomedical research due to the inability to effectively mimic conditions found in vivo. The gold standard for hypoxia work is the hypoxic chamber, but the tool requires hours for equilibration and is not effective at generating very low oxygen levels (3). As an example demonstrating this disadvantage, cancer tumor oxygenation can change in the span of minutes (4). Intermittent hypoxia, or the changing of oxygen over time, has been shown to be important in heart attack, stroke, and sleep apnea as well. Other microfluidic approaches, although offering more oxygen control, are often difficult to disseminate to other labs due to the requirement of specialized methods and equipment for their operation. In this work, a microfabricated technology has been developed to grant precise control the temporal and spatial oxygen concentration exposed to both cell monolayers in the multiwell plate as well as with 3-D cell-seeded constructs. The concept is adaptable to both pre-established and novel experiments depending on the needs of the researcher. The devices are simple to use and require minimal additional equipment beyond what is available to a standard cell culture lab.


2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Andrea J Morash ◽  
Jeremy M Lyle ◽  
Suzanne Currie ◽  
Justin D Bell ◽  
Kilian M Stehfest ◽  
...  

Abstract The endangered and range-restricted Maugean skate (Zearaja maugeana) is subjected to large environmental variability coupled with anthropogenic stressors in its endemic habitat, Macquarie Harbour, Tasmania. However, little is known about the basic biology/physiology of this skate, or how it may respond to future environmental challenges predicted from climate change and/or increases in human activities such as aquaculture. These skate live at a preferred depth of 5–15 m where the dissolved oxygen (DO) levels are moderate (~55% air saturation), but can be found in areas of the Harbour where DO can range from 100% saturation to anoxia. Given that the water at their preferred depth is already hypoxic, we sought to investigate their response to further decreases in DO that may arise from potential increases in anthropogenic stress. We measured oxygen consumption, haematological parameters, tissue–enzyme capacity and heat shock protein (HSP) levels in skate exposed to 55% dissolved O2 saturation (control) and 20% dissolved O2 saturation (hypoxic) for 48 h. We conclude that the Maugean skate appears to be an oxyconformer, with a decrease in the rate of O2 consumption with increasing hypoxia. Increases in blood glucose and lactate at 20% O2 suggest that skate are relying more on anaerobic metabolism to tolerate periods of very low oxygen. Despite these metabolic shifts, there was no difference in HSP70 levels between groups, suggesting this short-term exposure did not elicit a cellular stress response. The metabolic state of the skate suggests that low oxygen stress for longer periods of time (i.e. >48 h) may not be tolerable and could potentially result in loss of habitat or shifts in their preferred habitat. Given its endemic distribution and limited life-history information, it will be critical to understand its tolerance to environmental challenges to create robust conservation strategies.


2003 ◽  
Vol 23 (1) ◽  
pp. 359-369 ◽  
Author(s):  
Nobuhito Goda ◽  
Heather E. Ryan ◽  
Bahram Khadivi ◽  
Wayne McNulty ◽  
Robert C. Rickert ◽  
...  

ABSTRACT A classical cellular response to hypoxia is a cessation of growth. Hypoxia-induced growth arrest differs in different cell types but is likely an essential aspect of the response to wounding and injury. An important component of the hypoxic response is the activation of the hypoxia-inducible factor 1 (HIF-1) transcription factor. Although this transcription factor is essential for adaptation to low oxygen levels, the mechanisms through which it influences cell cycle arrest, including the degree to which it cooperates with the tumor suppressor protein p53, remain poorly understood. To determine broadly relevant aspects of HIF-1 function in primary cell growth arrest, we examined two different primary differentiated cell types which contained a deletable allele of the oxygen-sensitive component of HIF-1, the HIF-1α gene product. The two cell types were murine embryonic fibroblasts and splenic B lymphocytes; to determine how the function of HIF-1α influenced p53, we also created double-knockout (HIF-1α null, p53 null) strains and cells. In both cell types, loss of HIF-1α abolished hypoxia-induced growth arrest and did this in a p53-independent fashion. Surprisingly, in all cases, cells lacking both p53 and HIF-1α genes have completely lost the ability to alter the cell cycle in response to hypoxia. In addition, we have found that the loss of HIF-1α causes an increased progression into S phase during hypoxia, rather than a growth arrest. We show that hypoxia causes a HIF-1α-dependent increase in the expression of the cyclin-dependent kinase inhibitors p21 and p27; we also find that hypophosphorylation of retinoblastoma protein in hypoxia is HIF-1α dependent. These data demonstrate that the transcription factor HIF-1 is a major regulator of cell cycle arrest in primary cells during hypoxia.


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