Coordinate regulation of glycolysis by hypoxia in mammalian cells

Robin, Eugene D.; Murphy, Brian J.; Theodore, James

doi:10.1002/jcp.1041180311

Cited by 121 publications

(79 citation statements)

References 16 publications

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“…The antioxidant enzymes SOD, glutathione peroxidase (GP), and catalase are all two-to threefold higher in aerobic AM than in hypoxic PM (113), apparently reflecting the different levels of oxygenation. Similar changes in antioxidant enzyme phenotype occur when normally aerobic cells are cultured in hypoxia (48,59,101).…”

Section: Effects Of Hypoxia On Antioxidant Enzymesmentioning

confidence: 73%

“…Activities of the enzymes of oxidative phosphorylation and glycolysis differ significantly, with oxidative phosphorylation being higher in aerobic AM and glycolysis higher in hypoxic PM. Hypoxia decreases apparent expression of cytochrome oxidase in AM, a change in the electron transport system that would predispose to O 2 Ϫ formation (101). The antioxidant enzymes SOD, glutathione peroxidase (GP), and catalase are all two-to threefold higher in aerobic AM than in hypoxic PM (113), apparently reflecting the different levels of oxygenation.…”

Section: Effects Of Hypoxia On Antioxidant Enzymesmentioning

confidence: 99%

“…A number of mitochondrial enzymes, including cytochrome oxidase and manganese superoxide dismutase (Mn SOD), decrease in activity in hypoxia (81,101,113), with predicted effects on oxygen metabolism. Cellular hypoxia inhibits expression of the multisubunit cytochrome oxidase (complex IV), the final intramitochondrial site of oxidative phosphorylation.…”

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confidence: 99%

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Reactive species mechanisms of cellular hypoxia-reoxygenation injury

Jackson

2002

American Journal of Physiology-Cell Physiology

942

673

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Li, Chuanyu, and Robert M. Jackson. Reactive species mechanisms of cellular hypoxia-reoxygenation injury. Am J Physiol Cell Physiol 282: C227-C241, 2002; 10.1152/ajpcell.00112.2001.-Exacerbation of hypoxic injury after restoration of oxygenation (reoxygenation) is an important mechanism of cellular injury in transplantation and in myocardial, hepatic, intestinal, cerebral, renal, and other ischemic syndromes. Cellular hypoxia and reoxygenation are two essential elements of ischemia-reperfusion injury. Activated neutrophils contribute to vascular reperfusion injury, yet posthypoxic cellular injury occurs in the absence of inflammatory cells through mechanisms involving reactive oxygen (ROS) or nitrogen species (RNS). Xanthine oxidase (XO) produces ROS in some reoxygenated cells, but other intracellular sources of ROS are abundant, and XO is not required for reoxygenation injury. Hypoxic or reoxygenated mitochondria may produce excess superoxide (O 2 Ϫ ) and release H2O2, a diffusible long-lived oxidant that can activate signaling pathways or react vicinally with proteins and lipid membranes. This review focuses on the specific roles of ROS and RNS in the cellular response to hypoxia and subsequent cytolytic injury during reoxygenation.anoxia; ischemia; reperfusion BACKGROUND

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Section: Effects Of Hypoxia On Antioxidant Enzymesmentioning

confidence: 73%

Section: Effects Of Hypoxia On Antioxidant Enzymesmentioning

confidence: 99%

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Reactive species mechanisms of cellular hypoxia-reoxygenation injury

Jackson

2002

American Journal of Physiology-Cell Physiology

942

673

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“…For example, increased activities of HK and LDH have been reported during hypobaric hypoxia (400 mm Hg for 14 and 28 days) in guinea pig heart (Barrie and Harris, 1976) and severe intermittent hypoxia (8.5% oxygen, 12 hours/day for 4 weeks) in rat gastronemius muscle (Pastoris et al, 1994(Pastoris et al, , 1995. Similarly, exposure of mouse lung macrophage (LM) cells to hypoxia (pO 2 : 10-25 torr) for 96 hours led to increases in activities of glycolytic enzymes, including HK (⇑117%) and LDH (⇑151%) (Hance et al, 1980;Robin et al, 1984). The hypoxic treatment of rat myoblast (L8) cells resulted in increases in activities of all glycolytic enzymes investigated except HK (Hance et al, 1980).…”

Section: Discussionmentioning

confidence: 93%

Effects of continuous hypoxia on energy metabolism in cultured cerebro-cortical neurons

et al. 2008

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Mechanisms underlying hypoxia-induced neuronal adaptation have not been fully elucidated. In the present study we investigated glucose metabolism and the activities of glycolytic and TCA cycle enzymes in cerebro-cortical neurons exposed to hypoxia (3 days in 1% of O 2 ) or normoxia (room air). Hypoxia led to increased activities of LDH (251%), PK (90%), and HK (24%) and decreased activities of CS (15%) and GDH (34%). Neurons were incubated with [1-13 C]glucose for 45 and 120 min under normoxic or hypoxic (120 min only) conditions and 13 C enrichment determined in the medium and cell extract using 1 H-{ 13 C}-NMR. In hypoxia-treated neurons [3-13 C]lactate release into the medium was 428% greater than in normoxia-treated controls (45-min normoxic incubation) and total flux through lactate was increased by 425%. In contrast glucose oxidation was reduced significantly in hypoxia-treated neurons, even when expressed relative to total cellular protein, which correlated with the reduced activities of the measured mitochondrial enzymes. The results suggest that surviving neurons adapt to prolonged hypoxia by up-regulation of glycolysis and downregulation of oxidative energy metabolism, similar to certain other cell types. The factors leading to adaptation and survival for some neurons but not others remains to be determined.

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“…Low PHe in tumours is mainly a result of increased rate of glycolysis and poor vascularization, leading to inadequate removal of H+ (Vaupel et al, 1989). The rate of glycolysis is up-regulated in hypoxic tumour cells (Robin et al, 1984), and as anaerobic glycolysis leads to accumulation of lactic acid (Busa and Nuccitelli, 1984;Wike-Hooley et al, 1984;Vaupel et al, 1989) the PHe might be particularly low in the hypoxic regions of tumours (Kallinowski and Vaupel, 1988;Tannock and Rotin, 1989;Martin and Jain, 1994).…”

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confidence: 99%

Energy metabolism in human melanoma cells under hypoxic and acidic conditions in vitro

Skøyum

Eide²,

Berg³

et al. 1997

Br J Cancer

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Summary The response to treatment and the malignant progression of tumours are influenced by the ability of the tumour cells to withstand severe energy deprivation during prolonged exposure to hypoxia at normal or low extracellular pH (pHe). The objective of the present work was to demonstrate intertumour heterogeneity under conditions of microenvironment-induced energy deprivation and to investigate whether the heterogeneity can be attributed to differences in the capacity of the tumour cells to generate energy in an oxygen-deficient microenvironment. Cultures of four human melanoma cell lines (BEX-c, COX-c, SAX-c, WIX-c) were exposed to hypoxia in vitro at PHe 7.4, 7.0 or 6.6 for times up to 31 h by using the steel-chamber method. High-performance liquid chromatography was used to assess adenylate energy charge as a function of exposure time. Cellular rates of glucose uptake and lactate release were determined by using standard enzymatic test kits. The adenylate energy charge decreased with time under hypoxia in all cell lines. The decrease was most pronounced shortly after the treatment had been initiated and then tapered off. BEX-c and SAX-c showed a significantly higher adenylate energy charge under hypoxic conditions than did COX-c and WIX-c whether the PHe was 7.4, 7.0 or 6.6, showing that tumours can differ in the ability to avoid energy deprivation during microenvironmental stress. There was no correlation between the adenylate energy charge and the rates of glucose uptake and lactate release. Intertumour heterogeneity in the ability to withstand energy deprivation in an oxygen-deficient microenvironment cannot therefore be attributed mainly to differences in the capacity of the tumour cells to generate energy by anaerobic metabolism. The data presented here suggest that the heterogeneity is rather caused by differences in the capacity of the tumour cells to reduce the rate of energy consumption when exposed to hypoxia.

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Coordinate regulation of glycolysis by hypoxia in mammalian cells

Cited by 121 publications

References 16 publications

Reactive species mechanisms of cellular hypoxia-reoxygenation injury

Reactive species mechanisms of cellular hypoxia-reoxygenation injury

Effects of continuous hypoxia on energy metabolism in cultured cerebro-cortical neurons

Energy metabolism in human melanoma cells under hypoxic and acidic conditions in vitro

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