Striking Oxygen Sensitivity of the Peptidylglycine alpha-Amidating Monooxygenase (PAM) in Neuroendocrine Cell

SIMPSON PD; EIPPER BA; KATZ MJ,; GÁNDARA L; WAPPNER P; FISCHER R,; HODSON EJ; RATCLIFFE PJ,; MASSON N

JOURNAL OF BIOLOGICAL CHEMISTRY

AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

Año: 2015 vol. 290 p. 24891 - 24901

0021-9258

Interactions between biological pathways and molecular O2 require robust mechanisms for detecting and responding to changes in cellular O2 availability, in order to support O2 homeostasis. Peptidyl glycine alpha-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 from mild (7% O2) to severe (1% O2) hypoxia. In developing Drosophila melanogaster larvae, FMRF amidation in Tv cells is strikingly suppressed by hypoxia. Our findings have thus defined a novel monooxygenase-based O2 sensing mechanism that has the capacity to signal changes in O2 availability to peptidergic pathways.____________________________________