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Annasofia Anemone, Lorena Consolino, Francesca Arena, Martina Capozza, Dario Livio Longo
Cancer cells are characterized by a metabolic shift in cellular energy production, orchestrated by the transcription factor HIF-1α, from mitochondrial oxidative phosphorylation to increased glycolysis, regardless of oxygen availability (Warburg effect). The constitutive upregulation of glycolysis leads to an overproduction of acidic metabolic products, resulting in enhanced acidification of the extracellular pH (pHe ~ 6.5), which is a salient feature of the tumor microenvironment. Despite the importance of pH and tumor acidosis, there is currently no established clinical tool available to image the spatial distribution of tumor pHe...
February 14, 2019: Cancer Metastasis Reviews
Yuki Onishi, Manami Hiraiwa, Hikari Kamada, Takashi Iezaki, Takanori Yamada, Katsuyuki Kaneda, Eiichi Hinoi
An imbalance of branched-chain amino acids (BCAAs) in the brain may result in neuropathological conditions, such as autism spectrum disorders. The L-type amino acid transporter 1 (LAT1), encoded by the solute carrier transporter 7a5 ( Slc7a5 ) gene, is critical for maintaining normal levels of BCAAs in the brain. However, our understanding of the mechanisms that regulate the expression of LAT1/ Slc7a5 in neurons is currently limited. Here, we demonstrate that hypoxic conditions result in upregulated expression of Slc7a5 in differentiated neuronal cells (Neuro2A cells induced to differentiate using all- trans retinoic acid)...
February 2019: FEBS Open Bio
Yongdong Dai, Xiang Lin, Wenzhi Xu, Xiaona Lin, Qianmeng Huang, Libing Shi, Yibin Pan, Yinli Zhang, Yunshan Zhu, Chao Li, Lulu Liu, Songying Zhang
Endometriosis is associated with benign but adversely developed cysts in the extrauterine environment. The oxidative imbalanced environment induces DNA damage and affects cell cycle progression of endometrial stromal cells (ESCs) and endometrial epithelial cells, but how endometriotic cells maintain proliferation in the presence of oxidative stress is not clear. Growing evidence has indicated that the ectopic hypoxic microenvironment and oxidative stress can stimulate the growth of endometriotic cells, which is mainly due to the increase of HIF-1α...
February 13, 2019: Cell Death & Disease
Zucheng Luo, Fangfang Wu, Enxing Xue, Linlin Huang, Ping Yan, Xiaoyun Pan, Yulong Zhou
Bone marrow derived stem cells (BMSCs) transplantation are viewed as a promising therapeutic candidate for spinal cord injury (SCI). However, the inflammatory microenvironment in the spinal cord following SCI limits the survival and efficacy of transplanted BMSCs. In this study, we investigate whether injured neuronal cells derived exosomes would influence the survival of transplanted BMSCs after SCI. In order to mimic the microenvironment in SCI that the neuronal cells or transplanted BMSCs suffer in vivo, PC12 cells conditioned medium and PC12 cell's exosomes collected from H2 O2 -treated PC12 cell's culture medium were cultured with BMSCs under oxidative stress in vitro...
February 12, 2019: Cell Death & Disease
Nak-Kyun Soung, Hye-Min Kim, Yukihiro Asami, Dong Hyun Kim, Yangrae Cho, Ravi Naik, Yerin Jang, Kusic Jang, Ho Jin Han, Srinivas Rao Ganipisetti, Hyunjoo Cha-Molstad, Joonsung Hwang, Kyung Ho Lee, Sung-Kyun Ko, Jae-Hyuk Jang, In-Ja Ryoo, Yong Tae Kwon, Kyung Sang Lee, Hiroyuki Osada, Kyeong Lee, Bo Yeon Kim, Jong Seog Ahn
Hypoxia-inducible factor-1α (HIF-1α) mediates tumor cell adaptation to hypoxic conditions and is a potentially important anticancer therapeutic target. We previously developed a method for synthesizing a benzofuran-based natural product, (R)-(-)-moracin-O, and obtained a novel potent analog, MO-460 that suppresses the accumulation of HIF-1α in Hep3B cells. However, the molecular target and underlying mechanism of action of MO-460 remained unclear. In the current study, we identified heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) as a molecular target of MO-460...
February 12, 2019: Experimental & Molecular Medicine
Pinglan Lin, Ming Wu, Junyan Qin, Jing Yang, Chaoyang Ye, Chen Wang
BACKGROUND: Magnesium lithospermate B (MLB) can promote renal microcirculation. The aim of the current project was to study whether MLB improves renal hemodynamics, oxygen consumption and subsequently attenuates hypoxia in rats induced by 5/6th renal Ablation/Infarction(A/I). METHODS: Chronic renal failure (CRF) was induced in male SD rats by the 5/6 (A/I) surgery. 30 rats were randomly divided into three groups: sham group, 5/6 (A/I) + vehicle group (CRF group) and 5/6 (A/I) + MLB (CRF + MLB) group...
February 12, 2019: BMC Nephrology
C B Item, A Schanzer, T Metz, S Greber-Platzer, J Lischka
OBJECTIVES: Elevated levels of metabolites such as ammonia and propionylcarnitine in propionic acidemia (PA) lead to an increased reactive oxygen species (ROS) production which could activate and stabilize the epigenetic regulated hypoxia-inducible factor-1α (HIF-1α). In order to evaluate the DNA methylation status of the HIF-1α binding site in PA, we investigated the antioxidant gluthatione peroxidase 3 gene (GPX3) promoter region. DESIGN AND METHODS: Using leukocyte DNA extracted from bloodspots collected 2-4 days after birth from diet free newborns, the cytosine phosphodiester bond guanine (CpG) dinucleotides of a HIF-1α binding site (CGTTTTTTACG) in the promoter region of GPX3 was retrospectively analysed...
February 9, 2019: Clinical Biochemistry
Katarzyna Magierowska, Dominik Bakalarz, Dagmara Wójcik, Anna Chmura, Magdalena Hubalewska-Mazgaj, Sabina Licholai, Edyta Korbut, Slawomir Kwiecien, Zbigniew Sliwowski, Grzegorz Ginter, Tomasz Brzozowski, Marcin Magierowski
BACKGROUND AND PURPOSE: Besides hydrogen sulfide (H2 S) and nitric oxide (NO), carbon monoxide (CO) contributes to the maintenance of gastric mucosal integrity. We investigated increased CO bioavailability effects on time-dependent dynamics of gastric ulcer healing mediated by particular growth factors, anti-inflammatory and molecular pathways. EXPERIMENTAL APPROACH: Wistar rats with gastric ulcers induced by serosal acetic acid application (day 0) were treated i...
February 9, 2019: Biochemical Pharmacology
Ken Ling, Ancong Xu, Yunfei Chen, Xueyin Chen, Yiqing Li, Weici Wang
Restenosis is liable to occur following treatment with endovascular interventional therapy. Increasing evidence indicates that hydrogen sulfide (H2S) exhibits numerous physiological properties, including antioxidative and cardioprotective disease properties. Thus, the present study aimed to investigate the anti‑restenosis effects of H2S and its protective mechanisms. A balloon dilatation restenosis model was used, in which model Sprague‑Dawley rats were treated with sodium hydrosulfide (NaHS: A donor of H2S, 30 µmol/kg) by intraperitoneal injection for 4 weeks...
January 23, 2019: International Journal of Molecular Medicine
Amita Ajit, Santhoshkumar Thankayyan Retnabai, Lissy K Krishnan
Biotechnological interventions to engineer favorable biochemical environments that facilitate wound repair through quick attainment of vasculature are of immense demand. Potential of angiogenic factors (AF), notably vascular endothelial growth factor A (VEGF-A) and hypoxia-inducible factor-1α (Hif-1α) and the paracrine role of human adipose derived mesenchymal stromal cells (hADMSCs) in establishing vasculature has been reported. Independent application of AF or hADMSCs has led to clinical failure, pertaining to poor means of delivery, deprived bioavailability and insufficiency to drive adequate angiogenesis, respectively...
February 12, 2019: Tissue Engineering. Part C, Methods
Chao Liu, Shengfeng Li, Fawei Pang, Haiwei Wu, Li Chai, Cheng Liang, Dongsheng Zhang
OBJECTIVES: Salivary adenoid cystic carcinoma (SACC) is one of the most common malignant salivary gland tumors. Our study aims to investigate whether hypoxia-induced autophagy was up-regulated in the progression of SACC. MATERIALS AND METHODS: We performed differentially expressed gene analysis, pathway enrichment analysis and then calculated the correlation analysis on GSE59701 and GSE28996 datasets. The expression of HIF-1ɑ and MAP1LC3B was analyzed in the paraffin-embedded specimens by immunohistochemical method and in the hypoxic SACC-LM cells by immunofluorescence...
February 11, 2019: Oral Diseases
Zaira Rehman, Ammad Fahim, Attya Bhatti, Hajra Sadia, Peter John
The hypoxic tumor microenvironment is the major contributor of chemotherapy resistance in solid tumors. One of the key regulators of hypoxic responses within the cell is the hypoxia inducible factor-1α (HIF-1α) that is involved in transcription of genes promoting cell survival and chemotherapy resistance. Multidrug resistance gene-1 (MDR1) and Lysosome-associated protein transmembrane 4B-35 (LAPTM4B-35) are among those notable players which augment their responses to cellular hypoxia. MDR1 is the hypoxia responsive gene involved in multidrug resistance phenotype while LAPTM4B-35 is involved in chemotherapy resistance by stabilizing HIF-1α and overexpressing MDR1...
2019: PeerJ
Baoan Hong, Jingcheng Zhou, Kaifang Ma, Jiufeng Zhang, Haibiao Xie, Kenan Zhang, Lei Li, Lin Cai, Ning Zhang, Zhongyuan Zhang, Kan Gong
Tribbles pseudokinase 3 (TRIB3) is a member of the mammalian pseudokinase tribbles family and is involved in multiple biological processes. However, the role of TRIB3 in renal cell carcinoma (RCC) remains unclear. In this study, we aimed to elucidate the biological functions of TRIB3 in RCC and explore its underlying mechanisms. TRIB3 expression and its correlation with clinicopathological features was evaluated in 123 patients with RCC. A series of cytological experiments were performed to clarify the biological functions of TRIB3, and potential molecular regulatory mechanisms were explored using transcriptome sequencing...
2019: International Journal of Biological Sciences
Deng Huang, Li Cao, Le Xiao, Ju-Xian Song, Yu-Jun Zhang, Ping Zheng, Shu-Guo Zheng
Studies have shown that hypoxia can induce cytoskeletal injury and remodeling through the activation of the RhoA/ROCK signaling pathway by hypoxia-inducible factor-1α (HIF-1α). Our previous study confirmed that CAPZA1 can modulate EMT by regulating actin cytoskeleton remodeling. However, the relationship between HIF-1α and CAPZA1 has not been illustrated. Therefore, this study aimed to investigate the mechanism by which hypoxia induces the remodeling of the actin cytoskeleton by regulating CAPZA1 in HCC cells...
February 8, 2019: Cancer Letters
Hailong Chen, Jiuqin Zheng, Junjie Ma
BACKGROUND: In the search for treating neurological dysfunctions after spinal cord injury (SCI), methods of neuroprotection are of interest to intervene with the caspase pathway. OBJECTIVE: To evaluate the neuroprotective effects of vanillin in a rat model of spinal cord injury (SCI). METHODS: Rats were randomly assigned to one of three groups: a sham-operated group, and two groups where SCI was produced by ischemia/reperfusion which received either saline or vanillin (286 mg/kg, intraperitoneal [i...
February 4, 2019: Restorative Neurology and Neuroscience
Yongsheng Wang, Yinliang Qi, Xiang Wei, Shaolong Chen, Ning Jia, Qing Zhou, Sumei Zhang, Shuyu Gui, Yuan Wang
Hypoxia induces vigorous growth and a higher malignant phenotype in solid tumors. Hyperoxic treatment using hyperbaric oxygen (HBO) has previously been shown as a highly effective method to attenuate hypoxia. We aimed to investigate the effect of HBO on hypoxia-induced malignancy of lung cancer cells. Cobalt chloride (CoCl2 ) was used to induce chemical hypoxia in lung cancer cell line A549. Hypoxic inducible factor-1α (HIF-1α) expression, lactate dehydrogenase (LDH) activity, migration and invasion capacity, expression profiles of epithelial-mesenchymal transition (EMT) markers and apoptotic markers were assessed in CoCl2 -treated A549 cells, with or without HBO treatment...
February 10, 2019: Experimental Lung Research
Haiying Fu, Xueqin Ding, Wenjing Zhang, Y James Kang
Under hypoxic condition, copper (Cu) accumulates in cell nuclei, and regulates the activity of hypoxia-inducible factor-1 (HIF-1) through Cu-binding proteins (CuBPs). To understand the CuBPs in the nucleus, proteomic approach was undertaken to explore the dynamic changes of the CuBPs in response to hypoxia. Human umbilical vein endothelial cells (HUVECs) were treated with dimethyloxalylglycine in a final concentration of 100 μM for 4 h to induce hypoxia, resulting in the accumulation of HIF-1α and Cu in the nucleus...
February 9, 2019: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
Karolina Kowalska, Dominika Ewa Habrowska-Górczyńska, Kinga Anna Urbanek, Kamila Domińska, Agata Sakowicz, Agnieszka Wanda Piastowska-Ciesielska
Zearalenone (ZEA) - a fungal mycotoxin is reported to both cause the oxidative stress associated with death of cells as well as induction of the proliferation of cells, depending on its concentration and the type of cells. ZEA due to its structural similarity to naturally occurring estrogens is able to bind to estrogen receptors and triggers estrogen-associated signaling pathways. The aim of this study is to evaluate whether the induction of oxidative stress in normal epithelial prostate PNT1A cells is associated with estrogenic activity of ZEA...
February 7, 2019: Ecotoxicology and Environmental Safety
Min Deng, Yong-Ju Xue, Le-Rong Xu, Qiang-Wu Wang, Jun Wei, Xi-Quan Ke, Jian-Chao Wang, Xiao-Dong Chen
Colorectal cancer (CRC) is a common human malignancy, accounting for 600,000 death cases annually worldwide. Chrysophanol is a naturally occurring anthraquinone compound and exhibits anti-neoplastic activities. This study aims to explore the biological effects of chrysophanol on CRC metastasis and the relevant underlying mechanism. Cell proliferation assay, Wound scratch assay and Transwell invasion assay were used to examine the effect of chrysophanol on proliferation, migration and invasion of CRC cells. Hypoxia-inducible factor-1α (HIF-1α) shRNA was utilized to transfect CRC cells in order to examine the role of HIF-1α in chrysophanol suppression of hypoxia-induced epithelial to mesenchymal transition (EMT)...
February 8, 2019: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
Qi Yang, Xuejun Li
Cases with pituitary adenoma comprise 10-25% of intracranial neoplasm, being the third most common intracranial tumor, most of the adenomas are considered to be benign. About 35% of pituitary adenomas are invasive. This review summarized the known molecular basis of the invasiveness of pituitary adenomas. The study pointed out that hypoxia-inducible factor-1α, pituitary tumor transforming gene, vascular endothelial growth factor, fibroblast growth factor-2, and matrix metalloproteinases (MMPs, mainly MMP-2, and MMP-9) are core molecules responsible for the invasiveness of pituitary adenomas...
2019: Frontiers in Endocrinology
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