Expression of Leu-19 (CD56, N-CAM) and nitric oxide synthase (NOS) I in denervated and reinnervated human skeletal muscle

Neural cell adhesion molecule (N-CAM, Leu-19, CD 56) expression appears dur ing muscle fiber regeneration and after denervation. Sarcolemma-associated nitric oxide synthase (NOS) I, however, disappears from denervated myofiber s. The dynamics of expression of both proteins were studied in 5 cases of a cute/subacute denervation, 28 cases of chronic denervation with and without collateral reinnervation, 5 cases of the intermediate type spinal muscular atrophy (SMA 2), and in 2 normal biopsies. NOS I and its NADPH diaphorase (NADPHd) activity disappeared from the sarcolemma. region shortly after den ervation, and before the appearance of denervation. atrophy. N-CAM was foun d diffusely distributed in the sarcoplasm at the most severe phase of dener vation atrophy in the majority of highly atrophic fibers. During reinnervat ion, NOS I expression remained absent and in part of the cases the target/t argetoid phenomenon appeared. In parallel with the increase in volume of th e reinnervated muscle fibers, the intensity of N-CAM immunoreactivity decre ased progressively. After full restitution of muscle fiber caliber, the tar get/ targetoid phenomenon and N-CAM immunostaining disappeared completely, and, finally, NOS I reappeared in the sarcolemma region. The sarcolemmal ex pression of dystrophin and dystrophin-associated proteins was unchanged dur ing denervation. NOS I was completely absent in children with SMA 2, since the protein does not appear before 5 years of age in skeletal muscle, while N-CAM was very intensely expressed in the sarcoplasm of highly atrophic de nervated muscle fibers. In conclusion, this study suggests that innervation is an important factor for selective gene expression and positioning of NO S I and N-CAM in skeletal muscle and gives practical information for the as sessment of the phase and developmental stage of the denervation and reinne rvation process. Microsc. Res. Tech. 55:187-197, 2001. (C) 2001 Wiley-Liss, Inc.