Fenofibrate inhibits hypoxia‐inducible factor‐1 alpha and carbonic anhydrase expression through activation of AMP‐activated protein kinase/ HO ‐1/Sirt1 pathway in glioblastoma cells

2021 ◽  
Author(s):  
Chingju Lin ◽  
Sheng‐Wei Lai ◽  
Ching‐Kai Shen ◽  
Chao‐Wei Chen ◽  
Cheng‐Fang Tsai ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Carbonic Anhydrase ◽  
Hypoxia Inducible Factor ◽  
Glioblastoma Cells ◽  
Hypoxia Inducible Factor 1 ◽  
Amp Activated Protein Kinase

DEC1 (STRA13) protein expression relates to hypoxia- inducible factor 1-alpha and carbonic anhydrase-9 overexpression in non-small cell lung cancer

2003 ◽  
Vol 200 (2) ◽  
pp. 222-228 ◽  
Author(s):  
Alexandra Giatromanolaki ◽  
Michael I Koukourakis ◽  
Efthimios Sivridis ◽  
Helen Turley ◽  
Charles C Wykoff ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Carbonic Anhydrase ◽  
Protein Expression ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Hypoxia Inducible Factor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Hypoxia Inducible Factor 1 ◽  
Carbonic Anhydrase 9

scholarly journals Carbonic Anhydrase Inhibitors Targeting Metabolism and Tumor Microenvironment

Metabolites ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 412 ◽  
Author(s):  
Andrea Angeli ◽  
Fabrizio Carta ◽  
Alessio Nocentini ◽  
Jean-Yves Winum ◽  
Raivis Zalubovskis ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Carbonic Anhydrase ◽  
Drug Targets ◽  
Ph Regulation ◽  
Hypoxia Inducible Factor ◽  
Lead Compounds ◽  
Hypoxia Inducible Factor 1 ◽  
Ca Ix ◽  
Activation Of Transcription ◽  
Hif Pathway

The tumor microenvironment is crucial for the growth of cancer cells, triggering particular biochemical and physiological changes, which frequently influence the outcome of anticancer therapies. The biochemical rationale behind many of these phenomena resides in the activation of transcription factors such as hypoxia-inducible factor 1 and 2 (HIF-1/2). In turn, the HIF pathway activates a number of genes including those involved in glucose metabolism, angiogenesis, and pH regulation. Several carbonic anhydrase (CA, EC 4.2.1.1) isoforms, such as CA IX and XII, actively participate in these processes and were validated as antitumor/antimetastatic drug targets. Here, we review the field of CA inhibitors (CAIs), which selectively inhibit the cancer-associated CA isoforms. Particular focus was on the identification of lead compounds and various inhibitor classes, and the measurement of CA inhibitory on-/off-target effects. In addition, the preclinical data that resulted in the identification of SLC-0111, a sulfonamide in Phase Ib/II clinical trials for the treatment of hypoxic, advanced solid tumors, are detailed.

scholarly journals Chronic opioids regulate KATP channel subunit Kir6.2 and carbonic anhydrase I and II expression in rat adrenal chromaffin cells via HIF-2α and protein kinase A

2014 ◽  
Vol 307 (3) ◽  
pp. C266-C277 ◽  
Author(s):  
Shaima Salman ◽  
Alison C. Holloway ◽  
Colin A. Nurse
Keyword(s):  
Protein Kinase ◽  
Carbonic Anhydrase ◽  
Protein Kinase A ◽  
Chromaffin Cells ◽  
Time Course ◽  
Molecular Mechanisms ◽  
Hypoxia Inducible Factor ◽  
Neonatal Rat ◽  
Pcr Analysis ◽  
Kinase A

At birth, asphyxial stressors such as hypoxia and hypercapnia are important physiological stimuli for adrenal catecholamine release that is critical for the proper transition to extrauterine life. We recently showed that chronic opioids blunt chemosensitivity of neonatal rat adrenomedullary chromaffin cells (AMCs) to hypoxia and hypercapnia. This blunting was attributable to increased ATP-sensitive K+ (KATP) channel and decreased carbonic anhydrase (CA) I and II expression, respectively, and involved μ- and δ-opioid receptor signaling pathways. To address underlying molecular mechanisms, we first exposed an O2- and CO2-sensitive, immortalized rat chromaffin cell line (MAH cells) to combined μ {[d-Arg2,Ly4]dermorphin-(1–4)-amide}- and δ ([d-Pen2,5,P-Cl-Phe4]enkephalin)-opioid agonists (2 μM) for ∼7 days. Western blot and quantitative real-time PCR analysis revealed that chronic opioids increased KATP channel subunit Kir6.2 and decreased CAII expression; both effects were blocked by naloxone and were absent in hypoxia-inducible factor (HIF)-2α-deficient MAH cells. Chronic opioids also stimulated HIF-2α accumulation along a time course similar to Kir6.2. Chromatin immunoprecipitation assays on opioid-treated cells revealed the binding of HIF-2α to a hypoxia response element in the promoter region of the Kir6.2 gene. The opioid-induced regulation of Kir6.2 and CAII was dependent on protein kinase A, but not protein kinase C or calmodulin kinase, activity. Interestingly, a similar pattern of HIF-2α, Kir6.2, and CAII regulation (including downregulation of CAI) was replicated in chromaffin tissue obtained from rat pups born to dams exposed to morphine throughout gestation. Collectively, these data reveal novel mechanisms by which chronic opioids blunt asphyxial chemosensitivity in AMCs, thereby contributing to abnormal arousal responses in the offspring of opiate-addicted mothers.

scholarly journals Activation of AMP-activated Protein Kinase by Temozolomide Contributes to Apoptosis in Glioblastoma Cells via p53 Activation and mTORC1 Inhibition

2010 ◽  
Vol 285 (52) ◽  
pp. 40461-40471 ◽  
Author(s):  
Wen-bin Zhang ◽  
Zhuo Wang ◽  
Fei Shu ◽  
Yong-hua Jin ◽  
Hong-yi Liu ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Glioblastoma Cells ◽  
P53 Activation ◽  
Amp Activated Protein Kinase
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