Expression of Nitric Oxide Synthase Isoforms and Protein Kinase-Cθ in the Different Fibre Types and Alterations by Diabetes and EGb 761 Pretreatment

Abstract

Nitric oxide (NO) produced by nitric oxide synthase (NOS) from 1-arginine is a physiological modulator of skeletal muscle function and is involved in force development (Kobzik et al. 1994), oxidative metabolism (Kobzik et al. 1995) and regulation of glucose transport (Balon and Nadler 1994; Bedard et al. 1997; Kapur et al. 1997; Reid 1998). Several studies revealed that all three isoforms — NOSI (neuronal NOS), NOSII (inducible NOS) and NOSIII (endothelial NOS) — are expressed in skeletal muscle fibres (Kobzik et al. 1994 1995; Förstermann and Kleinert 1995; Park et al. 1996; Christova et al. 1997; Grozdanovic et al. 1997; Reid 1998; Gath et al.1996,1999) as well as in the myocard (for review see Buchwalow et al. 2001). Individual muscle fibres can express one or more NOS isoforms (e.g. Reid 1998). However, the expression of the NOS isoforms in skeletal muscle fibres still remains a matter of debate. The sensitivity of the used immunohistochemical technique could be a factor which effects the demonstration of an isoform in histological sections. For instance, there are contradictionary reports about whether the isoform NOSII can be expressed constitutively or only in diseased states (for review see Förstermann and Kleinert 1995; Gath et al. 1996,1999; Park et al. 1996; Buchwalow et al. 2001). Generally, NOSII was found to be inducible in macrophages by endotoxin and cytokines (for review see Förstermann and Kleinert 1995). Constitutive NOSII expression was detected in human skeletal muscles (Park et al. 1996), in skeletal muscles from guinea pigs (Gath et al. 1996), and in mouse skeletal muscles (Gath et al. 1999). To answer the question whether the NOSII expression is constitutive or not in skeletal muscle fibres, further studies are necessary.