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Post‐translational modification of peptidylglycine α‐amidating monooxygenase by intermittent hypoxia
Author(s) -
Kumar Ganesh K,
Prabhakar Nanduri R
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.960.4
Subject(s) - chemistry , biochemistry , monooxygenase , trypsin , enzyme , glycine , western blot , brainstem , amino acid , medicine , cytochrome p450 , gene
Peptidylglycine α‐amidating monooxygenase (PAM) catalyzes the conversion of glycine‐extended peptide precursors to biologically active α‐amidated peptides in a copper, ascorbate and molecular oxygen‐dependent manner. In this study, we investigated the effects of chronic intermittent (CIH) and sustained hypoxia (CSH) on PAM activity and expression in the rat brainstem. CIH but not comparable duration of CSH increased PAM activity (by ∼ 3‐fold) resulting in higher V max . CIH enhanced ascorbate‐, but not Cu 2+ ‐dependent enzyme activity. Western blot analyses showed that CIH increases the formation of low molecular weight with a concomitant decrease in high molecular weight PAM‐related proteins. CIH increased trypsin‐like activity (∼2‐fold) in the brainstem. Trypsin activated PAM in the control but not in CIH brainstem extracts. CIH increased ROS in the brainstem. Anti‐oxidants abolished CIH‐induced increases in PAM and trypsin‐like activities as well as proteolytic processing of PAM. Taken together, these observations suggest that CIH activates PAM in the rat brainstem by mechanism(s) involving ROS‐dependent post‐translational proteolytic processing of the enzyme (supported by NIH HL‐25830).