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Results for “Cell Hypoxia”

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At least 19 recordsLinked to original sources
PubMed1979

Inhibition of angiotensin converting enzyme activity in cultured endothelial cells by hypoxia.

Endothelial cells in tissue culture degrade bradykinin and convert angiotensin I to angiotensin II. These are both functions of a single dipeptidyl hydrolase, angiotensin converting enzyme. Monolayer cultures were prepared from human, rabbit, pig, and calf vessels. Angiotensin converting enzyme activity was assessed by adding either bradykinin or angiotensin I to the cells in culture flasks, and measuring residual peptide over time by radioimmunoassay. Peptide degradation was inhibited by the specific converting enzyme inhibitor, SQ 20881. The flasks were equilibrated with varying hypoxic gas mixtures: hypoxia rapidly (less than 2 min) decreased enzyme activity and room air restored it as rapidly. The extent to which activity was reduced was a direct function of PO2 (r = 0.93, P less than 0.001), and there was no enzyme activity below a PO2 of 30 mm Hg. Four preparations were studied with respect to decrease in enzyme activity by hypoxia: (a) intact cells in monolayer, (b) sonicated cells, (c) sonicated cells from which converting enzyme was partially dissolved by a detergent, and (d) purified converting enzyme. Hypoxia had progressively less of an inhibiting effect on the enzyme activity of the preparations as the degree of cell integrity decreased. Hypoxia inhibits angiotensin converting enzyme activity in cultured endothelial cells, but the effect of hypoxia is not on the enzyme per se, but appears to be a unique characteristic of the endothelial cell.

Animals↗
PubMed1979

Injury to primary cultures of rat heart endothelial cells by hypoxia and glucose deprivation.

Primary cultures of rat heart endothelial cells were subjected to simulated conditions of ischemia: hyposia and glucose deprivation for 4 and 24 hr. Cellular injury was evaluated by measuring changes in viability, total protein, cellular morphology, and leakage of cytoplasmic enzymes from the cells into the culture medium. Deprivation of oxygen and glucose for 4 or 24 hr did not lethally injure the cells as noted by no change in cell viability, morphology, and total protein when compared to controls. However, reversible or non-lethal cellular injury was produced as reflected by a significant release of lactate dehydrogenase (LDH) from the cells into the medium after treatment with hypoxia and glucose deprivation for 4 or 24 hr. When the cultures were deprived of glucose, but were oxygenated, cellular injury was not evident after 24 hr. Deprivation of oxygen but not glucose resulted in significant loss of LDH after 4 or 24 hr. When the cultures were allowed to recover after oxygen and glucose deprivation in complete medium containing 1000 mg glucose per 1 and a normal atmosphere of 20% O2, they had levels of LDH leakage comparable to those of control cultures.

Animals↗
PubMed1977

Cellular swelling and irreversible myocardial injury. Effects of polyethylene glycol and mannitol in perfused rat hearts.

Irreversible injury was produced in Langendorf-perfused rat hearts by 60 minutes of hypoxic, substrate-free perfusion at 37 C. Upon reoxygenation, hearts suddenly released large amounts of creatine phosphokinase (CPK) and over 60% of cells contained contraction bands and appeared irreversibly injured by light and electron microscopic criteria. Ten percent polyethylene glycol (PEG) or mannitol (420 mOsmol/liter) prevented or reduced swelling of rat heart slices incubated in vitro in the cold or under anoxic conditions. Both PEG and mannitol inhibited oxygen-induced CPK release after 60 minutes of hypoxia. Cells from protected hearts contained contraction bands but remained structurally intact. The results of this study provide evidence that cell swelling may play an important role in the pathogenesis of oxygen-induced enzyme release and irreversible myocardial cell injury.

Animals↗
PubMed1978

[Antibody-forming capacity of mouse spleen cells after hypoxic hypoxia and the administration of erythropoietin].

In CBA mice the absolute and relative (per 10(6) spleen cells) number of antibody-forming cells (AFC) in the spleen was cut by half on the 1st, 4th, and 7th days after acute hypoxia (12 hours, 6700 m), and on the 1st and 4th days after cessation of chronic hypoxia (16 days, 16 hours, 6700 m). The number of AFC in the spleen returned to the normal level on the 7th day after cessation of chronic hypoxia. Single or double erythropoietin injections caused approximately a 1.15--2-fold decrease in spleen AFC number in posthypoxic mice in comparison with control animals.

Animals↗
PubMed1977

Release of adenosine triphosphate from isolated adult heart cells in response to hypoxia.

1. Adult rat heart cells were isolated enzymically and ATP was identified in the cell suspension using the firefly luminescence technique. Adenosine 5'-triphosphate (ATP) was not detected from cell suspensions obtained from hearts which had been left asystolic for 10 min.2. It was found that ATP 0.34 +/- 0.22 muM/mg protein was released by cells kept in an oxygenated condition, while ATP 1.28 +/- 0.41 muM/mg protein was initially released by cells made hypoxic.3. Addition of Ca(2+) in a concentration of 2 mM caused cells to initially extrude ATP 0.40 +/- 0.14 muM/mg protein. This was attributed to an inotropic effect.4. Extracellular ATPase activity in the fluid suspension was partially characterized, giving a K(m) of 13 muM and a V/2 of hydrolysed ATP 18.3 muM/min at 37 degrees C. Q(10) was found to be 4 between 25 and 37 degrees C. Enzyme activity remained unaffected by either hypoxic conditions or ouabain.5. If these amounts of ATP are released from myocardial cells rendered hypoxic in vivo, then it must be concluded that ATP plays a principal role in the local control of myocardial blood flow.6. It is proposed that release of ATP occurs through the sarcolemma from an intracellular pool, and that alteration of the configuration of structural membrane protein controls the amounts of ATP extruded.

Adenosine Triphosphatases↗
PubMed1978

Effects of different growth conditions on survival after irradiation in hypoxia of human cells (NHIK 3025) in vitro.

Cell cycle kinetics and radiation response under hypoxic conditions were analyzed with human cells of the line NHIK 3025. The cells were either kept in continuous exponential growth by frequent reculturing, or went through log and plateau phase for each passage (recultured weekly). The cell cycle time for weekly recultured populations in early log phase was shorter than for cells in continous exponential growth. Cells in continuous exponential growth were more sensitive to radiation than cells in log phase. The difference in sensitivity was not due to partial synchrony of weekly recultured populations.

Cell Count↗
PubMed2026

Hypoxia reprograms VEGF signaling to differentially control ADAMTS2 and ADAMTS3 expression in endothelial cells.

ADAMTS2/-3, key metalloproteinases involved in collagen processing and extracellular matrix dynamics, remain insufficiently characterized in terms of their transcriptional regulation under hypoxic and pro-angiogenic conditions. In this study, we demonstrate that VEGF₁₆₅ robustly enhances ADAMTS2/-3 expression in endothelial cells, with hypoxia providing a striking amplification of this response. Bioinformatic analyses revealed that hypoxia and VEGF induced HIF-mediated and time-varying expression responses in ADAMTS2/-3. Using HUVECs exposed to CoCl₂-induced hypoxia, VEGF stimulation led to substantial increases in ADAMTS2 (approximately 19-fold at 3 h) and ADAMTS3 (approximately 46-fold at 3 h) mRNA levels, accompanied by concordant protein upregulation. Promoter-reporter assays revealed strong VEGF responsiveness in defined ADAMTS2 (-658/+112) and ADAMTS3 (-131/+40; -1340/+40) promoter fragments, particularly under hypoxic conditions. Pharmacological inhibition showed that JNK, MAPK/ERK, p38, and PI3K pathways each contributed partially to VEGF-mediated transcription, indicating multi-pathway convergence rather than single-pathway dependency. This finding is consistent with RNA-seq analyses showing that VEGF-related signaling is extensively re-regulated under hypoxic conditions. Extension of these analyses to MG-63 and SAOS-2 cell lines revealed modest but consistent VEGF-induced upregulation, supporting a tissue-independent regulatory axis. Collectively, these findings position ADAMTS2/-3 as potent hypoxia- and VEGF-responsive genes, uncovering their integration into HIF-1α-dependent transcriptional networks and VEGF-activated signaling cascades. This work highlights the relevance of ADAMTS2/-3 in angiogenesis-associated extracellular matrix remodeling and identifies them as promising biomarkers and potential therapeutic targets in hypoxia-driven vascular pathology.

Humans↗
PubMed1978

Bioenergetic pattern of isolated type II pneumocytes in air and during hypoxia.

The bioenergetic pattern of a cell clone derived from rat lung with ultrastructural and biochemical characteristics like those of type II pneumocytes (T-II-P), has been studied in a tissue culture system. During air cultivation, these cells have a high rate of aerobic and anaerobic glycolysis associated with high activities of two rate-limiting enzymes in glycolysis (pyruvate kinase [PyKi] and phosphofructokinase [PFK]). This is present despite the rates of oxygen consumption and activities of cytochrome oxidase (CyOx) similar to other lung cells. Presumably the high rate of aerobic glycolysis explains the substantial lactate production previously described in lung slices and in the intact perfused lung. Hypoxic cultivation results in a decrease in CyOx. Acute re-exposure to air does not restore the oxygen consumption to normal, presumably as a result of decreased mitochondrial O(2) utilization associated with decreased CyOx activity. As a result, hypoxically cultivated T-II-P cells have a decreased capacity for mitochondrial ATP generation in air as compared to air-cultivated cells. During hypoxia, aerobic and anaerobic glycolysis are further increased as well as the activities of PyKi and PFK. The high rate of glycolysis and high activities of PyKi and PFK in cultivated T-II-P appear to reflect intrinsic genetic regulation. The decreased CyOx activity and increased PyKi and PFK activities in hypoxic T-II-P appear to reflect alterations in enzyme biosynthesis/biodegradation regulated by O(2) availability.

Animals↗
PubMed2026

Transcriptomic Profiling Reveals NF-κB-Associated Immune Regulatory Signatures Underlying the Regenerative Effects of Hypoxia-Preconditioned Tendon Stem Cell-Derived Extracellular Vesicles.

Remodeling of the immune microenvironment is a critical determinant of tissue regeneration, yet the molecular programs associated with the enhanced therapeutic activity of hypoxia-preconditioned extracellular vesicles remain incompletely defined. In this study, we investigated the regenerative and immunomodulatory effects of hypoxia-preconditioned tendon stem cell-derived extracellular vesicles (Hypo-EVs) and employed transcriptomic profiling to identify molecular signatures associated with their biological activity. The therapeutic effects of Hypo-EVs were evaluated using a rat patellar tendon defect model and lipopolysaccharide-stimulated RAW 264.7 macrophages. Histological analysis, immunostaining, biomechanical testing, and reverse transcription-quantitative polymerase chain reaction were performed to assess tendon healing and macrophage polarization, while RNA sequencing was conducted in macrophages treated with Hypo-EVs or normoxia-derived EVs, followed by Gene Set Enrichment Analysis, Gene Ontology, and Kyoto Encyclopaedia of Genes and Genomes pathway analyses. Hypo-EVs significantly alleviated local inflammatory responses, improved collagen organization and biomechanical properties of repaired tendons, and promoted macrophage polarization toward a reparative M2 phenotype both in vivo and in vitro. Consistent with these biological effects, transcriptomic profiling revealed extensive remodeling of inflammation-related gene expression programs, including significant suppression of NF-κB, TNF, IL-17, and cytokine-cytokine receptor interaction pathways. Integrative bioinformatic analyses identified an NF-κB-associated immune-regulatory signature that distinguished Hypo-EV-treated macrophages from those receiving normoxic EVs. Mechanistically, Hypo-EVs attenuated NF-κB activation, as evidenced by reduced phosphorylation of p65 and IκBα, whereas TNF-α-mediated NF-κB activation partially diminished their macrophage-repolarizing effects. Collectively, these findings demonstrate that hypoxic preconditioning enhances the immunomodulatory and regenerative functions of tendon stem cell-derived EVs. Transcriptomic analyses identified an NF-κB-associated immune-regulatory signature linked to the biological activity of Hypo-EVs, providing a molecular framework for understanding EV-mediated immune modulation and supporting the development of transcriptome-guided molecular signatures for regenerative therapies targeting tendon immune homeostasis.

Animals↗
PubMed1976

Hypoxia and lung mast cells: influence of disodium cromoglycate.

Rats kept in 10% O2 for three or more weeks developed mast cell hyperplasia in the lungs, especially round the alveoli and the small peripheral blood vessels, which became thickened during chronic hypoxia. There was a significant correlation between the degree of right ventricular hypertrophy (RVH) and the numbers of alveolar and small vessel mast cells. However, mast cell hyperplasia developed more slowly than RVH. Daily treatment with disodium cromoglycate failed to prevent RVH in hypoxic conditions but was associated with retardation of growth in both hypoxic and control rats. Neither acute nor chronic hypoxia increased the degree of degranulation in the lung mast cells.

Animals↗
PubMed1977

Kinetics of erythroid and myeloid stem cells in post-hypoxia polycythaemia.

The number of erythroid burst-(BFU-E) and colony-forming units (CFU-E), as well as of myeloid-macrophage colony-forming units (CFU-C), has been evaluated in tibial marrow and spleen of ex-hypoxic polycythaemic mice, at sequential time intervals after the end of hypoxia. In both marrow and spleen, the kinetics of the CFU-E pool is characterized by a sharp fall from above normal to lower than normal values. BFU-E and CFU-C however rise from below normal to higher than normal levels. These results have been correlated with both the erythropoietin (Ep) and the erythropoietic activity curves. It is apparent that Ep levels largely control both the differentiation and the amplification of the CFU-E pool and it is suggested that Ep may act as a 'survival factor' at the CFU-E level and/or increase the flow of cells from BFU-E to CFU-E. The difference in response between CFU-E and BFU-E favours a clearcut distinction between these populations, whereas the similarity between the BFU-E and CFU-C response suggest a close relationship between these two cell populations. It is also of interest that the murine spleen functions as a large reservoir of erythroid microenvironment for hypoxia-induced stress erythropoiesis.

Animals↗
PubMed1976

[On the influence of hypoxia on the sinus endothelial cells of rat liver. A scanning and transmission electron microscopic investigation (author's transl)].

Fine structural alterations of liver sinusoids in young and adult albino rats breathing 6% oxygen in nitrogen at normal atmospheric pressure for periods from 3 to 30 h were described by use of TEM and SEM. After short-term hypoxia the fenestrated areas of endothelial cells were partially destroyed. After long--term hypoxia wide gaps could be visualized in the endothelium, too. In the liver specimens of all hypoxic animals electron lucent membrane bounded blebs arose from the endothelial lining. Cytoplasmic protrusions of hepatocytes bulged into the sinusoidal lumen. In the space of Disse and the sinusoidal lumen bleblike corpuscles and parts of cytoplasmic membrane being discharged from liver cell vacuoles could be observed. The find structure of liver sinusoids in hypoxia was very similar in young and adult albino rats. The findings suggest a discharge of metabolites and cellular components from endothelial cells and hepatocytes in a state of energetic insufficiency by forming cellular blebs and protrusions. It was supposed, that the combined effects of hypoxia and shearing of circulating blood were responsible for the development of holes and gaps in the endothelial lining.

Animals↗
PubMed1979

[Effect of hypoxia on the contractile activity of smooth muscle cells of the thoracic lymphatic duct].

Hypoxia (95% N2; 5% CO2) led to complete or partial inhibition of spontaneous contractile activity of isolated segment of the rat thoracic lymphatic duct, PO2 of perfused solution being 5--10 mm Hg. Reoxygenation restored rhythmical although more frequent contractions of the smooth muscle cells. Excitability of cells membrane tested with KCl, BaCl2, and noradrenaline during hypoxic period proved lower during this decreased PO2. Preliminary depolarization with KCl, BaCl2, and noradrenaline of cells membrane delayed the inhibition of contractile activity during hypoxia. Compared with the portal vein, lymphatic duct revealed a greater resistance to hypoxia. The hypoxia seems to affect first the smooth muscle cell membrane which leads to modification of the contraction character.

Adenosine Triphosphate↗
PubMed2026

Unbiased screen of human transcriptome reveals an unexpected role of 3'UTRs in translation initiation.

Although most eukaryotic mRNAs require a 5'-cap for translation initiation, some can also be translated through a poorly studied cap-independent pathway. Here we develop a circRNA-based system and unbiasedly identify more than 10,000 sequences in the human transcriptome that contain Cap-independent Translation Initiators (CiTIs). Surprisingly, most of the identified CiTIs are located in 3'UTRs, which mainly promote translation initiation in mRNAs bearing highly structured 5'UTR. Mechanistically, CiTI recruits several translation initiation factors including eIF3 and DHX29, which in turn unwind 5'UTR structures and facilitate ribosome scanning. Functionally, we show that the translation of HIF1A mRNA, an endogenous DHX29 target, is antagonistically regulated by its 5'UTR structure and a new 3'-CiTI in response to hypoxia. Consistently, deletion of 3'-CiTI suppresses cell growth in hypoxia and tumor progression in vivo. Collectively, our study uncovers a new regulatory mode for translation where the 3'UTR actively participate in the translation initiation.

Humans↗
PubMed1977

Quantitative characteristics of the Feyrter (APUD) cells of the neonatal rabbit lung in normoxia and chronic hypoxia.

Our studies show that the apparent number of Feyrter cells in the lung declines during the neonatal period in normoxic rabbits, and that in hypoxic animals a uniformly and significantly lower number of cells occurs as compared with the normoxic rabbits. There is some indication of degranulation of cells in the hypoxic groups. It is suggested that environmental and/or physiological factors associated with the start of extrauterine life, or lung development, may affect the apparent number and probable level of activity of these cells. These changes seem to be enhanced by hypoxia. Mast cells are scarce, and Feyrter cells are relatively more numerous along the airways. These cell types could possibly represent storage sites for 5-hydroxytryptamine, as suggested also by other investigators. Intraepithelial nerve fibres in bronchi and bronchioles were found but they were not limited to innervations of Feyrter cells or related cell bodies.

APUD Cells↗