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Striking Oxygen Sensitivity of the Peptidylglycine ?-Amidating Monooxygenase (PAM) in Neuroendocrine Cells.


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 ?-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.

SUBMITTER: Simpson PD 

PROVIDER: S-EPMC4598998 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Striking Oxygen Sensitivity of the Peptidylglycine α-Amidating Monooxygenase (PAM) in Neuroendocrine Cells.

Simpson Peter D PD   Eipper Betty A BA   Katz Maximiliano J MJ   Gandara Lautaro L   Wappner Pablo P   Fischer Roman R   Hodson Emma J EJ   Ratcliffe Peter J PJ   Masson Norma N  

The Journal of biological chemistry 20150819 41


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. Differ  ...[more]

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