ABSTRACT
Mitochondrial-derived oxidative injury contributes to cellular aging as well as to reperfusion-induced tissue damage. While the aging-heart suffers greater tissue damage following ischemia and reperfusion than the adult heart, the occurrence of aging-related alterations in mitochondrial oxidative metabolism in the elderly heart has remained uncertain. We determined if aging altered oxidative metabolism in either of the two populations of cardiac mitochondria, subsarcolemmal mitochondria (SSM) that reside beneath the plasma membrane or interfibrillar mitochondria (IFM) located between the myofibrils. SSM and IFM were isolated from 6-month adult and 24- and 28-month elderly Fischer 344 rat hearts. Aging-related alterations were limited to IFM, while SSM remained unaffected. Aging decreased the rate of oxidative phosphorylation in IFM, including when stimulated by electron donors specific for cytochrome oxidase. Cytochrome oxidase enzyme activity was decreased in IFM from aging hearts, while activity in SSM remained similar to adult controls. These findings allow future studies of aging-related decrements in oxidative function to focus upon IFM, while SSM provide an inherent control group of mitochondria that are free of aging-related alterations in oxidative function. The selective alteration of IFM during aging raises the possibility that the consequences of aging-induced mitochondrial dysfunction will be enhanced in specific subcellular regions of the senescent myocyte.
Subject(s)
Aging/physiology , Mitochondria, Heart/metabolism , Myocardium/cytology , Myocardium/metabolism , Oxidative Phosphorylation , Adenosine Diphosphate/metabolism , Animals , Ascorbic Acid/metabolism , Cell Respiration/drug effects , Citrate (si)-Synthase/metabolism , Electron Transport/drug effects , Electron Transport Complex IV/metabolism , Glutamic Acid/metabolism , Male , Mitochondria, Heart/enzymology , Mitochondria, Heart/ultrastructure , Myocardium/enzymology , Myocardium/ultrastructure , NADH Dehydrogenase/metabolism , Oxidative Phosphorylation/drug effects , Phosphatidylcholines , Phospholipids/metabolism , Rats , Rats, Inbred F344 , Sarcolemma/enzymology , Sarcolemma/metabolism , Sarcolemma/ultrastructure , Succinate Cytochrome c Oxidoreductase/metabolism , Uncoupling Agents/pharmacologyABSTRACT
We describe 2 patients with clinical syndromes suggestive of Wegener's granulomatosis: elevated titers of cytoplasmic antineutrophil cytoplasmic antibodies (cANCA), bronchocentric granulomatosis, and acute renal failure. A renal biopsy in one case showed crescentic glomerulonephritis and in the other case showed interstitial nephritis. These cases may reflect bronchocentric granulomatosis among a spectrum of diseases associated with cANCA. Use of cANCA may identify those patients with bronchocentric granulomatosis who require immunosuppressive therapy.
