title: Photoperiod-dependent regulation of carboxypeptidase E affects the selective processing of neuropeptides in the seasonal Siberian hamster (Phodopus sungorus).
abstract: The production of bioactive peptides from biologically inactive precursors involves extensive post-translational processing, including enzymatic cleavage by proteolytic peptidases. Endoproteolytic prohormone-convertases initially cleave the precursors of many neuropeptides at specific amino acid sequences to generate intermediates with basic amino acid extensions on their C-termini. Subsequently, the related exopeptidases, carboxypeptidases D and E (CPD and CPE), are responsible for removing these amino acids before the peptides achieve biological activity. We investigated the effect of photoperiod on the processing of the neuropeptide precursor pro-opiomelanocortin (POMC) and its derived neuropeptides, α-melanocyte-stimulating hormone (MSH) and β-endorphin (END), within the hypothalamus of the seasonal Siberian hamster (Phodopus sungorus). We thus compared hypothalamic distribution of CPD, CPE, α-MSH and β-END using immunohistochemistry and measured the enzyme activity of CPE and concentrations of C-terminally cleaved α-MSH in short-day (SD; 8 : 16 h light/dark) and long-day (LD; 16 : 8 h light/dark) acclimatised hamsters. Increased immunoreactivity (-IR) of CPE, as well as higher CPE activity, was observed in SD. This increase was accompanied by more β-END-IR cells and substantially higher levels of C- terminally cleaved α-MSH, as determined by radioimmunoassay. Our results suggest that exoproteolytic cleavage of POMC-derived neuropeptides is tightly regulated by photoperiod in the Siberian hamster. Higher levels of biological active α-MSH- and β-END in SD are consistent with the hypothesis that post-translational processing is a key event in the regulation of seasonal energy balance.
authors.affiliation: Department of Anatomy & Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. michaelhelwig@umaryland.edu
authors.forename: M
authors.initials: M
authors.lastname: Helwig
authors.forename: A
authors.initials: A
authors.lastname: Herwig
authors.forename: G
authors.initials: G
authors.lastname: Heldmaier
authors.forename: P
authors.initials: P
authors.lastname: Barrett
authors.forename: J G
authors.initials: JG
authors.lastname: Mercer
authors.forename: M
authors.initials: M
authors.lastname: Klingenspor
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D043423:Carboxypeptidase H / Q000378:metabolism*; D006224:Cricetinae; D008297:Male; D009479:Neuropeptides / Q000378:metabolism*; D017111:Phodopus / Q000378:metabolism / Q000502:physiology*; D017440:Photoperiod; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D012621:Seasons; D013379:Substrate Specificity; D000521:alpha-MSH / Q000378:metabolism; D001615:beta-Endorphin / Q000378:metabolism
chemical_list: D009479:Neuropeptides; D000521:alpha-MSH; D001615:beta-Endorphin; D011333:Pro-Opiomelanocortin; D043423:Carboxypeptidase H