Heme oxygenase-2 is present in the sarcolemma region of skeletal muscle fibers and is non-continuously co-localized with nitric oxide synthase-1

There is increasing evidence that the heme oxygenase-2 (HO-2)/carbon monoxi de (CO) pathway and the nitric oxide synthase (NOS)/nitric oxide (NO) pathw ay functionally cross-talk. Therefore, we investigated the appearance of HO -2 in mammalian skeletal muscles where NOS-1 is known to be expressed in hi gh quantities. Immunoblotting of rat hind limb extensor muscles extracts re vealed a single 36 kDa band demonstrating the existence of HO-2 in skeletal muscle and indicating the monospecifity of the antibody that was applied. Immunohistochemistry on healthy rat extensor hind limb muscles showed that HO-2 is present in satellite cells, endothelial cells of the vascular syste m, fibrocytes/fibroblasts but also fiber type-independently in extrafusal m yofibers either in association with the non-junctional sarcolemma region, o r in a subsarcolemmal network or, less prominently, in cross-striated strip es connected to longitudinally running lines. Combined HO-2 immunohistochem istry and NOS-1 histochemistry revealed an apparent co-localization of both molecules only in the non-junctional sarcolemma region of extrafusal type II myofibers outside costameres. In diseased muscles of mdx mice, HO-2 expr ession was not changed. In patients suffering from Duchenne's muscular dyst rophy, it was absent in the sarcolemma region. In conclusion, the HO-2/CO s ystem is present in mammalian skeletal muscle where it is non-continuously co-localized with the NOS-1/NO-system. This finding implicates an optionall y functional cross-talk between both gaseous signaling pathways.