Identification of Hypoxia‐inducible factor (HIF) stabilizer roxadustat and its possible metabolites in thoroughbred horses for doping control

2021 ◽  
Author(s):  
Binoy Mathew ◽  
Moses Philip ◽  
Zubair Perwad ◽  
Tajudheen K. Karatt ◽  
Marina Rodriguez Caveney ◽  
...  
Keyword(s):  
Hypoxia Inducible Factor ◽  
Doping Control ◽  
Thoroughbred Horses

In vitro studies of Hypoxia Inducible Factor‐ Prolyl Hydroxylase Inhibitors Daprodustat, Desidustat and Vadadustat for equine doping control

2021 ◽  
Author(s):  
Moses Philip ◽  
Abdul Khader Karakka Kal ◽  
Michael Benedict Subhahar ◽  
Tajudheen K. Karatt ◽  
Binoy Mathew ◽  
...  
Keyword(s):  
Hypoxia Inducible Factor ◽  
Prolyl Hydroxylase ◽  
Doping Control ◽  
In Vitro Studies

Study of cobalt doping control via various routes in thoroughbred horses

2021 ◽  
Author(s):  
Young Beom Kwak ◽  
Jundong Yu ◽  
Eo Jin Im ◽  
Bok Son Jeong ◽  
Hye Hyun Yoo
Keyword(s):  
Doping Control ◽  
Cobalt Doping ◽  
Thoroughbred Horses

Metabolic studies of hypoxia‐inducible factor stabilisers IOX2 , IOX3 and IOX4 (in vitro) for doping control

2021 ◽  
Author(s):  
Moses Philip ◽  
Binoy Mathew ◽  
Tajudheen K. Karatt ◽  
Zubair Perwad ◽  
Michael Benedict Subhahar ◽  
...  
Keyword(s):  
Hypoxia Inducible Factor ◽  
Doping Control ◽  
Metabolic Studies

Vascular adaptations to hypoxia: molecular and cellular mechanisms regulating vascular tone

2007 ◽  
Vol 43 ◽  
pp. 105-120 ◽  
Author(s):  
Michael L. Paffett ◽  
Benjimen R. Walker
Keyword(s):  
Vascular Tone ◽  
Cellular Proliferation ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Hypoxia Inducible Factor ◽  
Systemic Circulation ◽  
Cellular Mechanisms ◽  
Hypoxia Inducible Factor 1 ◽  
Pulmonary Vasoconstriction ◽  
Adaptive Mechanisms ◽  
Adaptive Processes

Several molecular and cellular adaptive mechanisms to hypoxia exist within the vasculature. Many of these processes involve oxygen sensing which is transduced into mediators of vasoconstriction in the pulmonary circulation and vasodilation in the systemic circulation. A variety of oxygen-responsive pathways, such as HIF (hypoxia-inducible factor)-1 and HOs (haem oxygenases), contribute to the overall adaptive process during hypoxia and are currently an area of intense research. Generation of ROS (reactive oxygen species) may also differentially regulate vascular tone in these circulations. Potential candidates underlying the divergent responses between the systemic and pulmonary circulations may include Nox (NADPH oxidase)-derived ROS and mitochondrial-derived ROS. In addition to alterations in ROS production governing vascular tone in the hypoxic setting, other vascular adaptations are likely to be involved. HPV (hypoxic pulmonary vasoconstriction) and CH (chronic hypoxia)-induced alterations in cellular proliferation, ionic conductances and changes in the contractile apparatus sensitivity to calcium, all occur as adaptive processes within the vasculature.

HIF1-α-Mediated Gene Expression Induced by Vitamin B1 Deficiency

2013 ◽  
Vol 83 (3) ◽  
pp. 188-197 ◽  
Author(s):  
Rebecca L. Sweet ◽  
Jason A. Zastre
Keyword(s):  
Gene Expression ◽  
Thiamine Deficiency ◽  
Glucose Transporter ◽  
Neuroblastoma Cell ◽  
Hypoxia Inducible Factor ◽  
Clinical Manifestations ◽  
Vitamin B1 ◽  
Low Oxygen ◽  
Glucose Transporter 1 ◽  
Metabolic Intermediates

It is well established that thiamine deficiency results in an excess of metabolic intermediates such as lactate and pyruvate, which is likely due to insufficient levels of cofactor for the function of thiamine-dependent enzymes. When in excess, both pyruvate and lactate can increase the stabilization of the hypoxia-inducible factor 1-alpha (HIF-1α) transcription factor, resulting in the trans-activation of HIF-1α regulated genes independent of low oxygen, termed pseudo-hypoxia. Therefore, the resulting dysfunction in cellular metabolism and accumulation of pyruvate and lactate during thiamine deficiency may facilitate a pseudo-hypoxic state. In order to investigate the possibility of a transcriptional relationship between hypoxia and thiamine deficiency, we measured alterations in metabolic intermediates, HIF-1α stabilization, and gene expression. We found an increase in intracellular pyruvate and extracellular lactate levels after thiamine deficiency exposure to the neuroblastoma cell line SK-N-BE. Similar to cells exposed to hypoxia, there was a corresponding increase in HIF-1α stabilization and activation of target gene expression during thiamine deficiency, including glucose transporter-1 (GLUT1), vascular endothelial growth factor (VEGF), and aldolase A. Both hypoxia and thiamine deficiency exposure resulted in an increase in the expression of the thiamine transporter SLC19A3. These results indicate thiamine deficiency induces HIF-1α-mediated gene expression similar to that observed in hypoxic stress, and may provide evidence for a central transcriptional response associated with the clinical manifestations of thiamine deficiency.

Characteristic expression pattern of hypoxia inducible factor 2 alpha mutation-related paragangliomas

2015 ◽  
Vol 122 (03) ◽  
Author(s):  
S Fliedner ◽  
U Shankavaram ◽  
A Elkahloun ◽  
H Lehnert ◽  
K Pacak
Keyword(s):  
Expression Pattern ◽  
Hypoxia Inducible Factor

Mechanisms underlying pituitary microvascular remodelling in thoroughbred horses during the annual reproductive cycle

2014 ◽  
Author(s):  
Angus Yeomans ◽  
Nichol Thompson ◽  
Jennifer Castle-Miller ◽  
David O Bates ◽  
Domingo Tortonese
Keyword(s):  
Reproductive Cycle ◽  
Annual Reproductive Cycle ◽  
Thoroughbred Horses
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