Nitric oxide and manifestations of lesions of skin and gastrointestinal tract in zinc deficiency.
Information is conflicting as to whether nitric oxide plays a role in the pathogenic mechanisms of zinc deficiency. Our series of research using a rat model demonstrated that inducible nitric oxide synthase in the intestine is upregulated by zinc deficiency when challenged by the injection of IL-1alpha, and the systemic administration of nitric oxide synthase inhibitor attenuates both intestinal damage and inflammatory skin lesions induced by zinc deficiency. Evidence from both transcription and translation levels indicates that inducible nitric oxide synthase, one of three nitric oxide synthase isoforms, has already been induced in the skin and intestine of zinc-deficient animals, whereas it is not generally expressed in normal tissues. On the other hand, total nitric oxide synthase activity in the intestine of zinc-deficient animals is significantly lower than that in controls, indicating that zinc deficiency may induce a potential vulnerability to nitric oxide rather than an absolute increase of nitric oxide synthase activities. Tissue zinc and metallothionein levels are significantly decreased in zinc-deficient rats, suggesting lowered antioxidative capability. Whether nitric oxide is destructive in inflammation may depend on the status of homeostasis such as the zinc level of tissues and the balance between the three nitric oxide synthase components, although identifying an absolute increase of nitric oxide production is of importance. Defining the role of nitric oxide provides the rationale for new strategies in zinc deficiency.
Department of Pediatric Surgery, Osaka University Medical School, Suita, Japan.
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Okada
D017209:Apoptosis; D005767:Gastrointestinal Diseases / Q000209:etiology*; D006801:Humans; D007422:Intestines / Q000201:enzymology; D008668:Metallothionein / Q000032:analysis; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D012867:Skin / Q000201:enzymology; D012871:Skin Diseases / Q000209:etiology*; D015032:Zinc / Q000032:analysis / Q000172:deficiency
D009569:Nitric Oxide; D008668:Metallothionein; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D015032:Zinc