A case of serendipity*

Forrester, T

doi:10.1007/s11302-007-9090-y

Cited by 13 publications

(7 citation statements)

References 52 publications

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“…During the first wave of enthusiasm for adenosine as a vasodilator substance linked to exercise hyperemia in the 1960s and early 1970s, the possibility that either ADP or ATP was the major vasodilating metabolite released by the contracting muscles also emerged (163)(164)(165). Many of the issues associated with determining adenosine concentrations in or near contracting skeletal muscles also apply to ADP and ATP.…”

Section: Atpmentioning

confidence: 99%

Regulation of Increased Blood Flow (Hyperemia) to Muscles During Exercise: A Hierarchy of Competing Physiological Needs

Joyner

Casey

2015

Physiological Reviews

582

513

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LJoyner MJ, Casey DP. Regulation of Increased Blood Flow (Hyperemia) to Muscles During Exercise: A Hierarchy of Competing Physiological Needs. Physiol Rev 95: 549 -601, 2015; doi:10.1152/physrev.00035.2013.-This review focuses on how blood flow to contracting skeletal muscles is regulated during exercise in humans. The idea is that blood flow to the contracting muscles links oxygen in the atmosphere with the contracting muscles where it is consumed. In this context, we take a top down approach and review the basics of oxygen consumption at rest and during exercise in humans, how these values change with training, and the systemic hemodynamic adaptations that support them. We highlight the very high muscle blood flow responses to exercise discovered in the 1980s. We also discuss the vasodilating factors in the contracting muscles responsible for these very high flows. Finally, the competition between demand for blood flow by contracting muscles and maximum systemic cardiac output is discussed as a potential challenge to blood pressure regulation during heavy large muscle mass or whole body exercise in humans. At this time, no one dominant dilator mechanism accounts for exercise hyperemia. Additionally, complex interactions between the sympathetic nervous system and the microcirculation facilitate high levels of systemic oxygen extraction and permit just enough sympathetic control of blood flow to contracting muscles to regulate blood pressure during large muscle mass exercise in humans.

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Section: Atpmentioning

confidence: 99%

Regulation of Increased Blood Flow (Hyperemia) to Muscles During Exercise: A Hierarchy of Competing Physiological Needs

Joyner

Casey

2015

Physiological Reviews

582

513

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“…Such actions of released ATP are rarely considered in experiments with cultured or isolated cells. Mechanical and chemical stimulation also promotes the release of ATP in vivo from skeletal muscle (53), heart (54), and erythrocytes (55) and in the nervous system, including the trigeminal and dorsal root ganglia (56, 57), ventral medulla (58), cochlea (59), and glia (60). …”

Section: Cellular Release Of Atpmentioning

confidence: 99%

Basal Release of ATP: An Autocrine-Paracrine Mechanism for Cell Regulation

2010

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Cells release adenosine triphosphate (ATP), which activates plasma membrane–localized P2X and P2Y receptors and thereby modulates cellular function in an autocrine or paracrine manner. Release of ATP and the subsequent activation of P2 receptors help establish the basal level of activation (sometimes termed “the set point”) for signal transduction pathways and regulate a wide array of responses that include tissue blood flow, ion transport, cell volume regulation, neuronal signaling, and host-pathogen interactions. Basal release and autocrine or paracrine responses to ATP are multifunctional and evolutionarily conserved, and they provide an economical means for the modulation of cell, tissue, and organismal biology.

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“…Thereby, it is possible that ATP plays a vital role in promoting or preventing malignant transformation. The amount of extracellular ATP is negligible in healthy tissues . By contrast, ATP accumulates at high levels in tumor sites, reaching hundreds of micromoles in the host‐tumor interface .…”

Section: Introductionmentioning

confidence: 99%

Extracellular ATP promotes breast cancer invasion and epithelial‐mesenchymal transition via hypoxia‐inducible factor 2α signaling

et al. 2019

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Extracellular ATP has been shown to play an important role in invasion and the epithelial‐mesenchymal transition (EMT) process in breast cancer; however, the mechanism is unclear. Here, by using a cDNA microarray, we demonstrated that extracellular ATP could stimulate hypoxia‐inducible factor (HIF) signaling and upregulate hypoxia‐inducible factor 1/2α (HIF‐1/2α) expression. After knocking down HIF‐1/2α using siRNA, we found that ATP‐driven invasion and EMT were significantly attenuated via HIF2A‐siRNA in breast cancer cells. By using ChIP assays, we revealed that the biological function of extracellular ATP in invasion and EMT process depended on HIF‐2α direct targets, among which lysyl oxidase‐like 2 (LOXL2) and matrix metalloproteinase‐9 (MMP‐9) mediated ATP‐driven invasion, and E‐cadherin and Snail mediated ATP‐driven EMT, respectively. In addition, using silver staining and mass spectrometry, we found that phosphoglycerate kinase 1 (PGK1) could interact with HIF‐2α and mediate ATP‐driven HIF‐2α upregulation. Furthermore, we demonstrated that expressions of HIF‐2α and its target proteins could be regulated via ATP by AKT‐PGK1 pathway. Using a Balb/c mice model, we illustrated the function of HIF‐2α in promoting tumor growth and metastasis in vivo. Moreover, by exploring online databases, we found that molecules involved in ATP‐HIF‐2α signaling were highly expressed in human breast carcinoma tissues and were associated with poor prognosis. Altogether, these findings suggest that extracellular ATP could promote breast carcinoma invasion and EMT via HIF‐2α signaling, which may be a potential target for future anti–metastasis therapy.

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A case of serendipity*

Cited by 13 publications

References 52 publications

Regulation of Increased Blood Flow (Hyperemia) to Muscles During Exercise: A Hierarchy of Competing Physiological Needs

Regulation of Increased Blood Flow (Hyperemia) to Muscles During Exercise: A Hierarchy of Competing Physiological Needs

Basal Release of ATP: An Autocrine-Paracrine Mechanism for Cell Regulation

Extracellular ATP promotes breast cancer invasion and epithelial‐mesenchymal transition via hypoxia‐inducible factor 2α signaling

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