Inducible nitric oxide synthase in human diseases - PubMed (original) (raw)

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Inducible nitric oxide synthase in human diseases

K D Kröncke et al. Clin Exp Immunol. 1998 Aug.

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Fig. 1

Fig. 1

Schematic structure of the human inducible nitric oxide synthase (iNOS) 5′ flanking region (a), the upstream enhancer region (b), and the human iNOS mRNA (c). (a) The main transcriptional start site is denoted at position + 1. Several potential transcription factor binding sites are indicated. The TATA box begins at −30. TATA-independent iNOS transcripts have alternative splice sites at positions −221, −36 and +191 in the 5′ UTR of the gene. Possible start codons (▪) of open reading frames are located at −256, −65, −45, −40 and +187. (b) Structure of the distal part of the human iNOS promoter which seems to be a cytokine-responsive enhancer element. This promoter region (−10.9 to −8.7 kb) increases iNOS transcription orientation independently by a factor of 2. It contains multiple binding sites for transcription factors, which are activated in response to either IFN-γ (IRF-1, STAT1) or IL-1β (AP-1, IRF-1). (c) Alternative splicing of human iNOS mRNA. The ratios of alternatively to constitutively spliced mRNA differ among tissues and depend on activation by cytokines. *Truncated iNOS with exon 5 deletion abundant in human cerebellum [29]. γIRE, IFN-γ-responsive element; NF, nuclear factor; AABS, activator binding site; SSRE, shear stress responsive element; E, exon; I, intron; IRF, interferon regulatory factor; STAT, signal transducer and activator transcription.

Fig. 2

Fig. 2

Current data suggest that inducible nitric oxide synthase (iNOS) expression and NO production in humans are much more tightly regulated than in rodents. In addition, human cells appear to be less susceptible to NO than rodent cells. Thus, in humans NO-mediated gene regulatory effects may be of more relevance than cytotoxic effects.

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