PORPHYRIN LOADING OF LIPOFUSCIN GRANULES IN INFLAMED STRIATED-MUSCLE

To further the understanding of oxidative effects on inflammation inju ry to muscle fiber structure, fluorescent imaging analysis of human st riated muscle tissues from a variety of inflammatory or postinflammato ry etiologies was undertaken in a search for accumulated coproporphyri n, a red autofluorescent byproduct of heme biosynthesis that would the oretically be formed under oxidative insult. Using a differential exci tation method of in situ analysis, porphyrin autofluorescence was dete cted in intact fibers within the context of the yellow autofluorescent subsarcolemmal Lipofuscin granules. Relative measurements of porphyri n concentration in the granules from different patients indicated that the acute/subacute inflammatory specimens grouped significantly highe r than the more chronic inflammatory and non pathological specimens. M yoglobin was also found to be associated with the granules. Myoglobin heme iron could potentially serve as a Fenton reagent for the intracel lular generation of hydroxyl radicals, which are responsible for the o xidation of the porphyrinogens. High-performance liquid chromatography analysis of extracted dense particles revealed coproporphyrin as the sole porphyrin present. The observation of coproporphyrin within lipof uscin granules previously unreported, suggests that lipofuscin accumul ation in striated muscle may begin under conditions of acute oxidative stress, as marked by the oxidation of extramitochondrial porphyrinoge ns that are immediately incorporated into the granules.