Hypoxia increases glucose transporter 1 expression in bovine corpus luteum at the early luteal stage

Nishimura, Ryo; Hasegawa, Hiroki; Yamashita, Masamichi; Ito, Norihiko; Okamoto, Yoshiharu; Takeuchi, Takashi; Kubo, Tomoaki; Iga, Kosuke; Kimura, Koji; Hishinuma, Mitsugu; Okuda, Kiyoshi

doi:10.1292/jvms.17-0284

Cited by 11 publications

(6 citation statements)

References 46 publications

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“…Similarly in the present study, low oxygen levels induced the expression of GLUT1 (Glucose transporter 1) and GLUT 3 (Glucose transporter 3), which mediate the glucose uptake into cells. Increased expression of GLUT1 was found in early luteal cells in response to low oxygen levels (3% O2), however, mid luteal cells failed to show such a response ( Nishimura et al, 2017 ). In addition, substantial down-regulation of TXNIP expression further confirms the increased glucose metabolism at LOL.…”

Section: Discussionmentioning

confidence: 96%

Low Oxygen Levels Induce Early Luteinization Associated Changes in Bovine Granulosa Cells

et al. 2018

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During follicle maturation, oxygen levels continuously decrease in the follicular fluid and reach lowest levels in the preovulatory follicle. The current study was designed to comprehensively understand effects of low oxygen levels on bovine granulosa cells (GC) using our established estrogen active GC culture model. As evident from flow cytometry analysis the viability of GC was not found to be affected at severely low oxygen condition (1% O2) compared to normal (atmospheric) oxygen condition (21% O2). Estimations of hormone concentrations using competitive radioimmunoassay revealed that the production of estradiol and progesterone was significantly reduced at low oxygen condition. To understand the genome-wide changes of gene expression, mRNA microarray analysis was performed using Affymetrix’s Bovine Gene 1.0 ST Arrays. This resulted in the identification of 1104 differentially regulated genes of which 505 were up- and 599 down-regulated under low oxygen conditions. Pathway analysis using Ingenuity pathway analyzer (IPA) identified 36 significantly affected (p < 0.05) canonical pathways. Importantly, pathways like “Estrogen-mediated S-phase Entry” and “Cyclins and Cell Cycle Regulation” were found to be greatly down-regulated at low oxygen levels. This was experimentally validated using flow cytometry based cell cycle analysis. Up-regulation of critical genes associated with angiogenesis, inflammation, and glucose metabolism, and down-regulation of FSH signaling, steroidogenesis and cell proliferation indicated that low oxygen levels induced early luteinization associated changes in granulosa cells. Identification of unmethylated CpG sites in the CYP19A1 promoter region suggests that granulosa cells were not completely transformed into luteal cells under the present low oxygen in vitro condition. In addition, the comparison with earlier published in vivo microarray data indicated that 1107 genes showed a similar expression pattern in granulosa cells at low oxygen levels (in vitro) as found in preovulatory follicles after the LH surge (in vivo). Overall, our findings demonstrate for the first time that low oxygen levels in preovulatory follicles may play an important role in supporting early events of luteinization in granulosa cells.

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Section: Discussionmentioning

confidence: 96%

Low Oxygen Levels Induce Early Luteinization Associated Changes in Bovine Granulosa Cells

et al. 2018

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“…HK2 is expressed explicitly in the synovial lining of RA and has a regulatory effect on the severity of arthritis, bone and cartilage damage in mice, and the invasion function of FLS 31 . The microenvironment of the inflammatory joints also appears hypoxic and nutrient deficient 32 , which stimulates a significant increase in glycolysis 33 , mainly by inducing the expression of HIF-1α and GLUT1 34 . Increased expression of GLUT1 leads to an increase in glucose uptake, activation of cell proliferation, and aggravation of the disease course.…”

Section: Discussionmentioning

confidence: 99%

Shikonin induces programmed death of fibroblast synovial cells in rheumatoid arthritis by inhibiting energy pathways

Pang

Liu

et al. 2021

Sci Rep

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Shikonin is the main component of the traditional Chinese medicine comfrey, which can inhibit the activity of PKM2 by regulating glycolysis and ATP production. Rheumatoid arthritis synovial cells (RA-FLSs) have been reported to increase glycolytic activity and have other similar hallmarks of metabolic activity. In this study, we investigated the effects of shikonin on glycolysis, mitochondrial function, and cell death in RA-FLSs. The results showed that shikonin induced apoptosis and autophagy in RA-FLSs by activating the production of reactive oxygen species (ROS) and inhibiting intracellular ATP levels, glycolysis-related proteins, and the PI3K-AKT-mTOR signaling pathway. Shikonin can significantly reduce the expression of apoptosis-related proteins, paw swelling in rat arthritic tissues, and the levels of inflammatory factors in peripheral blood, such as TNF-α, IL-6, IL-8, IL-10, IL-17A, and IL-1β while showing less toxicity to the liver and kidney.

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“…The expressions of SLC2A1 and SLC2A3 genes are activated by HIF-1 modulation. These genes encode glucose transporters, GLUT1 and GLUT3 ( Nishimura et al, 2017 ). These transporters are upregulated to transfer more glucose to enhance the process of glycolysis.…”

Section: The Roles Of Hypoxic Hif-1 Signaling In Cardiovascular Diseamentioning

confidence: 99%

Novel Therapeutic Targets for Hypoxia-Related Cardiovascular Diseases: The Role of HIF-1

Liu¹,

Galli

Wang

et al. 2020

Front. Physiol.

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Insufficient oxygen availability (hypoxia) is a precursor to numerous cardiovascular diseases, including atherosclerosis, pulmonary hypertension, and heart failure. The main site of hypoxic injury in the human body is the mitochondria, where oxygen acts as the final electron acceptor in the process of oxidative phosphorylation. Hypoxia-inducible factor (HIF) is activated in hypoxic conditions and acts as an important modulator of diverse target genes in the human body. The downstream genes of HIF include vital modulators of cardiovascular-related signaling pathways. Therefore, it is hypothesized that HIF represents a potential therapeutic target for the treatment and prevention of cardiovascular diseases. In this short review, we introduce the pathophysiology of hypoxic injury in cardiovascular disease, and we conclude from convincing evidence that HIF can modulate relevant cardioprotective signaling pathways.

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Hypoxia increases glucose transporter 1 expression in bovine corpus luteum at the early luteal stage

Cited by 11 publications

References 46 publications

Low Oxygen Levels Induce Early Luteinization Associated Changes in Bovine Granulosa Cells

Low Oxygen Levels Induce Early Luteinization Associated Changes in Bovine Granulosa Cells

Shikonin induces programmed death of fibroblast synovial cells in rheumatoid arthritis by inhibiting energy pathways

Novel Therapeutic Targets for Hypoxia-Related Cardiovascular Diseases: The Role of HIF-1

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