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 monoxide (CO) pathway and the nitric oxide synthase (NOS)/nitric oxide (NO) pathway functionally cross-talk. Therefore, we investigated the appearance of HO-2 in mammalian skeletal muscles where NOS-1 is known to be expressed in high quantities. Immunoblotting of rat hind limb extensor muscles extracts revealed 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 system, fibrocytes/fibroblasts but also fiber type-independently in extrafusal myofibers either in association with the non-junctional sarcolemma region, or in a subsarcolemmal network or, less prominently, in cross-striated stripes connected to longitudinally running lines. Combined HO-2 immunohistochemistry 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 expression was not changed. In patients suffering from Duchenne's muscular dystrophy, it was absent in the sarcolemma region. In conclusion, the HO-2/CO system is present in mammalian skeletal muscle where it is non-continuously co-localized with the NOS-1/NO-system. This finding implicates an optionally functional cross-talk between both gaseous signaling pathways.