Gene expression in low oxygen tension.
Low oxygen tension is a feature of many physiologic and pathologic conditions, including wound healing, fibrosis, and neoplasia. Increasing evidence suggests that low oxygen tension induces the transcription of a number of genes, and that this process depends on the cellular context. The proteins synthesized from these genes enable cells to adapt to the hypoxic environment and/or to fulfill their functional roles. The regulatory regions responsible for the induction of erythropoietin gene transcription and synthesis in response to hypoxia/anemia appear to be cis-acting deoxyribonucleic acid sequences located within the 5' and 3' flanking regions of the erythropoietin gene. Other proteins induced by hypoxia include cytokines (platelet-derived growth factor-beta chain, endothelin-1, transforming growth factor-beta), enzymes (tyrosine hydroxylase, glycolytic enzymes), and stress proteins. The molecular mechanisms of the hypoxia-induced expression of these genes are poorly understood. A heme protein may act as the oxygen tension sensor, or the redox state of certain nuclear transcription factors may function as second messengers.
Helfman
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Department of Dermatology and Cutaneous Surgery, University of Miami School of Medicine, FL 33136.
Falanga
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V
D000818:Animals; D015687:Cell Hypoxia; D016207:Cytokines / Q000096:biosynthesis*; D004921:Erythropoietin / Q000096:biosynthesis*; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D014158:Transcription, Genetic
D016207:Cytokines; D004921:Erythropoietin