Striking Oxygen Sensitivity of the Peptidylglycine α-Amidating Monooxygenase (PAM) in Neuroendocrine Cells |
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| Authors: | Peter D Simpson Betty A Eipper Maximiliano J Katz Lautaro Gandara Pablo Wappner Roman Fischer Emma J Hodson Peter J Ratcliffe Norma Masson |
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| Institution: | From the ‡Centre for Cellular and Molecular Physiology, University of Oxford, Oxford OX3 7BN, United Kingdom.;§Department of Neuroscience, University of Connecticut Health Center, Farmington, Connecticut 06030.;¶Fundacion Instituto Leloir, C1405BWE Buenos Aires, Argentina, and ;‖Target Discovery Institute, University of Oxford, Oxford OX3 7FZ, United Kingdom |
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| Abstract: | Interactions between biological pathways and molecular oxygen require robust mechanisms for detecting and responding to changes in cellular oxygen availability, to support oxygen homeostasis. Peptidylglycine α-amidating monooxygenase (PAM) catalyzes a two-step reaction resulting in the C-terminal amidation of peptides, a process important for their stability and biological activity. Here we show that in human, mouse, and insect cells, peptide amidation is exquisitely sensitive to hypoxia. Different amidation events on chromogranin A, and on peptides processed from proopiomelanocortin, manifest similar striking sensitivity to hypoxia in a range of neuroendocrine cells, being progressively inhibited from mild (7% O2) to severe (1% O2) hypoxia. In developing Drosophila melanogaster larvae, FMRF amidation in thoracic ventral (Tv) neurons is strikingly suppressed by hypoxia. Our findings have thus defined a novel monooxygenase-based oxygen sensing mechanism that has the capacity to signal changes in oxygen availability to peptidergic pathways. |
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| Keywords: | copper monooxygenase hypoxia hypoxia-inducible factor (HIF) peptide hormone secretion |
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