University of pisa, sant’anna school and university of oxford Researchers discovered enzymatic oxygen sensor in humans identical to plant enzymes controlling hypoxia
Researchers of University of Pisa, Sant’Anna School Life Sciences Institute and University of Oxford discovered an enzymatic oxygen sensor in humans that is functionally identical to plant cysteine oxidases, the enzymes that control responses to hypoxia in plants. The human and plant enzymes convert the N-terminal cysteine in substrate proteins to cysteine sulfinic acid, a modification that ultimately targets the proteins for degradation. The study has been published in Science journal.
Traditionally, plants have the capacity to produce oxygen. The ability to sense and respond to changes in oxygen levels is critical for most forms of life. Plants respond to hypoxia, often caused by submergence, by expressing a specific set of genes that contribute to acclimation. Genes induced by low oxygen include those encoding enzymes for carbohydrate metabolism pathway that is required for survival. Targeting the hypoxia (as an inadequate supply of oxygen) and oxygen-sensing mechanisms open a new route to the investigation of adaptive responses to hypoxia and the treatment of inflammatory diseases and cancer as hypoxia and expression of Hypoxia-inducible factors HIF-1α and HIF-2α are characteristic features of all solid tumors.
Scientists found that ADO (2-aminoethanethiol dioxygenase) conserved enzymatic oxygen sensor in multicellular eukaryotes leads to a better understanding of adaptive responses to hypoxia and that its activity extends to other N-cysteine proteins including the angiogenic cytokine interleukin-32.
Given the original assignment of ADO as a cysteamine dioxygenase, scientists also examined competition of N-cysteine peptide dioxygenation by free cysteamine and cysteine, but found inhibition only at high concentrations of these metabolites. Further investigations sought to determine whether ADO-mediated, oxygen-dependent regulation of human proteins extended beyond the identified RGS proteins.
“This oxygen sensing system conserved across biological kingdoms allows both plant and animal cells to sense and respond to changes in oxygen levels - an amazing ability central to the survival of most forms of life” – said Professor Francesco Licausi (University of Pisa).
“As oxygen sensing is impaired in many human diseases, like cancer, our findings could pave the way to new therapeutic interventions – said Beatrice Giuntoli, a researcher at the University of Pisa. We identified this type of cysteine oxidation in animals and identified the enzyme ADO producing more rapid responses to hypoxic conditions. Neither ADO nor HIF, however, is mutually exclusive - the results predict that both the ADO and HIF systems will interact to produce responses to hypoxia”.
“Plants and humans need oxygen sensing mechanisms and RGS4 and RGS5 have been implicated in oxygen homeostasis in mammals through effects on the cardiovascular system and angiogenesis– said Professor Pierdomenico Perata (Sant’Anna School). Through the stabilization of hypoxia-inducible factor-1 (HIF-1), we have shown that ADO is functionally identical to plant cysteine oxidases, enzymes that control responses to hypoxia in plants”.
Norma Masson, Thomas P. Keeley, Beatrice Giuntoli, Mark D. White,Mikel Lavilla Puerta, Pierdomenico Perata, Richard J. Hopkinson, Emily Flashman, Francesco Licausi, Peter J. Ratcliffe. Conserved N-terminal cysteine dioxygenases transduce responses to hypoxia in animals and plants. Science, 6448: 65-69
Photo Archive: PlantLab - oxygen sensor
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