Comparative study on the distribution and expression of Neuroglobin and Hypoxia-inducible factor-1α in the telencephalon of yak and cattle

The telencephalon refers to the most highly developed and anterior part of the forebrain, consisting mainly of the cerebral hemispheres. The study determined Neuroglobin (Ngb) and Hypoxia-inducible factor (HIF-1α) expression in the telencephalon of yak and cattle, and compare the expression and distribution pattern of Ngb and HIF-1α in the two animals. Immunohistochemistry (IHC), quantitative real-time Polymerase Chain Reaction (qRT-PCR), and Western blot (WB) were employed to investigate Ngb and Hif-1α expression in the telencephalon of yak and cattle. mRNA and protein expressions of Ngb and HIF-1α showed positive in different tissues of the yak and cattle telencephalon. Ngb expression in tissues of the yak recorded higher as compare to cattle while HIF-1α expression was found higher in cattle than yak. The HIF-1α expression in some tissues of yak telencephalon was consistent with the cattle. The results documented that HIF-1α may have a direct or indirect synergistic effect on Ngb expression in the yak telencephalon to improve hypoxia adaptation. It is suggested that yak may need more Ngb expression for adaptation, but the expression of HIF-1α seems to be down-regulated during long-term adaptation, and the specific causes of this phenomenon needs to be further verified.

Multi-Omics Analysis of Mammary Metabolic Changes in Dairy Cows Exposed to Hypoxia

Hypoxia exposure can cause a series of physiological and biochemical reactions in the organism and cells. Our previous studies found the milk fat rate increased significantly in hypoxic dairy cows, however, its specific metabolic mechanism is unclear. In this experiment, we explored and verified the mechanism of hypoxia adaptation based on the apparent and omics results of animal experiments and in vitro cell model. The results revealed that hypoxia exposure was associated with the elevation of AGPAT2-mediated glycerophospholipid metabolism. These intracellular metabolic disorders consequently led to the lipid disorders associated with apoptosis. Our findings update the existing understanding of increased adaptability of dairy cows exposure to hypoxia at the metabolic level.

A pair of long intergenic non-coding RNA LINC00887 variants act antagonistically to control Carbonic Anhydrase IX transcription upon hypoxia in tongue squamous carcinoma progression

Background Long noncoding RNAs (lncRNAs) are important regulators in tumor progression. However, their biological functions and underlying mechanisms in hypoxia adaptation remain largely unclear. Results Here, we established a correlation between a Chr3q29-derived lncRNA gene and tongue squamous carcinoma (TSCC) by genome-wide analyses. Using RACE, we determined that two novel variants of this lncRNA gene are generated in TSCC, namely LINC00887_TSCC_short (887S) and LINC00887_TSCC_long (887L). RNA-sequencing in 887S or 887L loss-of-function cells identified their common downstream target as Carbonic Anhydrase IX (CA9), a gene known to be upregulated by hypoxia during tumor progression. Mechanistically, our results showed that the hypoxia-augmented 887S and constitutively expressed 887L functioned in opposite directions on tumor progression through the common target CA9. Upon normoxia, 887S and 887L interacted. Upon hypoxia, the two variants were separated. Each RNA recognized and bound to their responsive DNA cis-acting elements on CA9 promoter: 887L activated CA9’s transcription through recruiting HIF1α, while 887S suppressed CA9 through DNMT1-mediated DNA methylation. Conclusions We provided hypoxia-permitted functions of two antagonistic lncRNA variants to fine control the hypoxia adaptation through CA9.

Characterization of EPO H131S as a Key Mutation Site in the Hypoxia-adaptive Evolution of Gymnocypris Dobula

Erythropoietin (EPO) is a glycoprotein hormone involved in proerythropoiesis, antioxidation and antiapoptosis. It also contributes to cellular immune function in high-altitude species, such as the schizothoracine fish Gymnocypris dobula (G. dobula). Six mutation sites previously identified in EPO from G. dobula (GD-EPO) were injected into zebrafish embryos and their effects were compared with EPO from the low-altitude schizothoracine Schizothorax prenanti (S. prenanti). The key mutation site in GD-EPO was identified as H131S. Under hypoxic conditions, the levels of superoxide dismutase and malondialdehyde were decreased, whereas that of nitric oxide was increased in zebrafish injected with GD-EPO compared with those injected with S. prenanti-EPO (SP-EPO). The results suggest that EPO in high-altitude schizothoracine species is both antioxidative and antiapoptotic, driven by the H131S mutation site. Thus, this enhanced the ability of this species to adapt to the high-altitude hypoxic environment. These results provide a basis for investigating further the hypoxia adaptation mechanisms of teleosts.

Mitochondrial creatine kinase 1 in non-small cell lung cancer progression and hypoxia adaptation

Background Hypoxia is a prominent feature of solid cancer. This research aims to expose the role of mitochondrial creatine kinase 1 (CKMT1) in non-small cell lung cancer (NSCLC) progression and hypoxia adaptation. Methods The mRNA and protein expression of CKMT1 in NSCLC tissues were detected by using GEPIA web, immunohistochemistry and qRT-PCR. For hypoxia, cells were exposed to the 1% O2 atmosphere. The protein levels of HIF-1α and CKMT1 in H1650 and H1299 cells exposed to hypoxia were determined by western blot. The roles of CKMT1 on the proliferation, invasion and hypoxia adaptation of NSCLC cells were measured by CCK8, colony formation and transwell assays. Luciferase activity assay and HIF1 specific inhibitor (LW6) assay indicated the related function of hypoxia and CKMT1. Results CKMT1 was highly expressed in NSCLC tissues, and the high level of CKMT1 was significantly correlated with the high pathological grade of NSCLC. Knockdown of CKMT1 inhibited the cell proliferation and invasion of H1650 and H1299 cells, which could be rescued by hypoxia. Hypoxia induced the accumulation of HIF-1α and the expression of CKMT1 in H1650 and H1299 cells. Furthermore, HIF-1 as a transcription factor of CKMT1, could up-regulated the expression of CKMT1 under hypoxia. Conclusions In summary, CKMT1 has the potential as a target for NSCLC hypoxic targeted therapy.

Transcriptome analysis of the liver of Eospalax fontanierii under hypoxia

Hypoxia can induce cell damage, inflammation, carcinogenesis, and inhibit liver regeneration in non-adapted species. Because of their excellent hypoxia adaptation features, subterranean rodents have been widely studied to clarify the mechanism of hypoxia adaptation. Eospalax fontanierii, which is a subterranean rodent found in China, can survive for more than 10 h under 4% O2 without observable injury, while Sprague-Dawley rats can survive for less than 6 h under the same conditions. To explore the potential mechanism of hypoxia responses in E. fontanierii, we performed RNA-seq analysis of the liver in E. fontanierii exposed to different oxygen levels (6.5% 6h, 10.5% 44h, and 21%). Based on the bioinformatics analysis, 39,439 unigenes were assembled, and 56.78% unigenes were annotated using public databases (Nr, GO, Swiss-Prot, KEGG, and Pfam). In total, 725 differentially expressed genes (DEGs) were identified in the response to hypoxia; six with important functions were validated by qPCR. Those DEGs were mainly involved in processes related to lipid metabolism, steroid catabolism, glycolysis/gluconeogenesis, and the AMPK and PPAR signaling pathway. By analyzing the expression patterns of important genes related to energy associated metabolism under hypoxia, we found that fatty acid oxidation and gluconeogenesis were increased, while protein synthesis and fatty acid synthesis were decreased. Furthermore, the upregulated expression of specific genes with anti-apoptosis or anti-oxidation functions under hypoxia may contribute to the mechanism by which E. fontanierii tolerates hypoxia. Our results provide an understanding of the response to hypoxia in E. fontanierii, and have potential value for biomedical studies.

Mitochondrial creatine kinase 1 in non-small cell lung cancer progression and hypoxia adaptation

Background Hypoxia is a prominent feature of solid cancer. This research aims to expose the role of mitochondrial creatine kinase 1 (CKMT1) in non-small cell lung cancer (NSCLC) progression and hypoxia adaptation. Methods The mRNA and protein expression of CKMT1 in NSCLC tissues and cells were detected using GEPIA web, immunohistochemistry, qRT-PCR and western blot. Cells were exposed to a hypoxic chamber with atmosphere containing 5% CO2, 1% O2 and residual N2. The protein levels of HIF-1α and CKMT1 in H1650 and H1299 cells exposed to hypoxia were determined by western blot. Luciferase activity assay and HIF1 specific inhibitor (LW6) assay indicated the related function of HIF-1 and CKMT1. The role of CKMT1 to NSCLC cells biological function on hypoxic condition was measured by CCK8, colony formation, transwell and apoptosis assay. Results CKMT1 was highly expressed in NSCLC tissues and cells using GEPIA web, immunohistochemistry, qRT-PCR and western blot. Hypoxia induced the accumulation of HIF-1α and the expression of CKMT1 in H1650 and H1299 cells. The results of luciferase activity assay and HIF1 specific inhibitor (LW6) assay indicated that HIF-1, as a transcription factor of CKMT1, up-regulated the expression of CKMT1 under hypoxic conditions. Further, knockdown of CKMT1 inhibited the cell proliferation and invasion of H1650 and H1299 cells, which could be rescued by hypoxia. Conclusions In summary, CKMT1 has the potential as a target for NSCLC hypoxic targeted therapy.