Compartmentalization of non-adenine nucleotides in anoxic cardiac myocytes.
Loss of 5'-nucleotides from cardiac myocytes is a distinguishing feature of myocardial ischemia. Previous work has documented dislocations of metabolic processes mediated by both purine and pyrimidine nucleotides, especially the adenine nucleotides. This study was designed to establish the extent of anoxia-induced depletion of non-adenine nucleotides in the cytosolic compartment of heart muscle cells. Cardiac myocytes were incubated aerobically (O(2)) or anoxically (N(2)) for 30 or 60 min; anoxic cells at both time points were reoxygenated for 10 min. Roughly 85-90% of cytosine triphosphate (CTP) and uridine triphosphate (UTP) were cytosolic under aerobic conditions, compared with 62% of guanosine triphosphate (GTP) and 90% of adenosine triphosphate (ATP) under similar conditions. Similarly, the total cytidine and uridine nucleotide pool of aerobic myocytes was 70-90% cytosolic vs. 61% of total guanine nucleotides and 78% of total adenine nucleotides. After the onset of anoxia, cytosolic nucleotides (principally the triphosphate forms) were quickly degraded. Reoxygenation of anoxic myocytes for 10 min allowed some recovery of ATP, GTP, and CTP, but very little recovery of UTP. The recovered nucleotide appeared almost exclusively in the cytosol. These results support the concept that non-adenine nucleotides could reach critically low levels in anoxic or ischemic heart in advance of adenine nucleotides. The importance of the depletion of non-adenine nucleotides is discussed in terms of the energetic needs of the myocyte, and the need for the cell to drive G-protein-coupled reactions, lipid synthesis, and glycogenesis.
Geisbuhler
Timothy P
TP
Department of Physiology, A.T. Still University, 800 West Jefferson Street, Kirksville, MO 63501, USA. tgeisbuhler@atsu.edu
D000332:Aerobiosis / Q000502:physiology; D000693:Anaerobiosis / Q000502:physiology; D000818:Animals; D002458:Cell Fractionation / Q000379:methods; D015687:Cell Hypoxia / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000502:physiology; D010100:Oxygen / Q000502:physiology; D011685:Purine Nucleotides / Q000378:metabolism*; D011742:Pyrimidine Nucleotides / Q000378:metabolism*; D051381:Rats
D011685:Purine Nucleotides; D011742:Pyrimidine Nucleotides; D010100:Oxygen