In light of the relevance of therapeutic hypothermia to stroke treatment, we investigated whether 5'-adenosine monophosphate (AMP)-dependent cooling affords protection from ischemic brain injury. We show that hypothermia by AMP is because of adenosine A1 receptor (A1R) activation and is not invariantly associated with hypotension. Inhibition of ecto-5'-nucleotidase-dependent constitutive degradation of brain extracellular AMP by methylene-ADP (AMPCP) also suffices to prompt A1R-dependent hypothermia without hypotension. Both intraischemic and postischemic hypothermia by AMP or AMPCP reduce infarct volumes and mortality of mice subjected to transient middle cerebral artery occlusion. Data disclose that AMP-dependent hypothermia is of therapeutic relevance to treatment of brain ischemia.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3564206 | PMC |
| http://dx.doi.org/10.1038/jcbfm.2012.181 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Adipocyte HIF2α functions as a thermostat via PKA Cα regulation in beige adipocytes.
Nat Commun
June 2022
Center for Adipocyte Structure and Function, Institute of Molecular Biology and Genetics, School of Biological Sciences, Seoul National University, Seoul, South Korea.
Thermogenic adipocytes generate heat to maintain body temperature against hypothermia in response to cold. Although tight regulation of thermogenesis is required to prevent energy sources depletion, the molecular details that tune thermogenesis are not thoroughly understood. Here, we demonstrate that adipocyte hypoxia-inducible factor α (HIFα) plays a key role in calibrating thermogenic function upon cold and re-warming.
View Article and Find Full Text PDFAIDA directly connects sympathetic innervation to adaptive thermogenesis by UCP1.
Nat Cell Biol
March 2021
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, China.
The sympathetic nervous system-catecholamine-uncoupling protein 1 (UCP1) axis plays an essential role in non-shivering adaptive thermogenesis. However, whether there exists a direct effector that physically connects catecholamine signalling to UCP1 in response to acute cold is unknown. Here we report that outer mitochondrial membrane-located AIDA is phosphorylated at S161 by the catecholamine-activated protein kinase A (PKA).
View Article and Find Full Text PDFDiscontinued stimulation of cardiomyocytes provides protection against hypothermia-rewarming-induced disruption of excitation-contraction coupling.
Exp Physiol
June 2018
Department of Physiology & Biomedical Engineering, Mayo Clinic, Rochester, MN, USA.
New Findings: What is the central question of this study? Will discontinued stimulation of isolated cardiomyocytes (asystole) during hypothermia mitigate hypothermia-rewarming-induced cytosolic Ca overload? What is the main finding and its importance? Mimicking asystole or hypothermic cardiac arrest by discontinued stimulation of cardiomyocytes during hypothermia resulted in normal contractile function after rewarming. This result suggests that asystole during severe hypothermia provides protection from hypothermia-rewarming-induced contractile dysfunction in cardiomyocytes.
Abstract: After exposure of spontaneously beating hearts or electrically stimulated isolated cardiomyocytes to hypothermia-rewarming (H/R), cardiac dysfunction or alteration in excitation-contraction coupling, respectively, is a consequence.
The Inside Story of Adenosine.
Int J Mol Sci
March 2018
Dipartimento di Biologia, Unità di Biochimica, Via San Zeno 51, 56127 Pisa, Italy.
Several physiological functions of adenosine (Ado) appear to be mediated by four G protein-coupled Ado receptors. Ado is produced extracellularly from the catabolism of the excreted ATP, or intracellularly from AMP, and then released through its transporter. High level of intracellular Ado occurs only at low energy charge, as an intermediate of ATP breakdown, leading to hypoxanthine production.
View Article and Find Full Text PDFHypothermia/rewarming disrupts excitation-contraction coupling in cardiomyocytes.
Am J Physiol Heart Circ Physiol
June 2016
Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota; and
Hypothermia/rewarming (H/R) is poorly tolerated by the myocardium; however, the underlying intracellular basis of H/R-induced cardiac dysfunction remains elusive. We hypothesized that in cardiomyocytes, H/R disrupts excitation-contraction coupling by reducing myofilament Ca(2+) sensitivity due to an increase in cardiac troponin I (cTnI) phosphorylation. To test this hypothesis, isolated rat cardiomyocytes (13-15 cells from 6 rats per group) were electrically stimulated to evoke both cytosolic Ca(2+) ([Ca(2+)]cyto) and contractile (sarcomere shortening) responses that were simultaneously measured using an IonOptix system.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!