Effect of hypothalamic proline-rich peptide (PRP-1) on neuronal and bone marrow cell apoptosis.
The AGAPEPAEPAQPGVY proline-rich peptide (PRP-1) was isolated from neurosecretory granules of the bovine neurohypophysis; it is produced by N. supraopticus and N. paraventricularis. It has been shown that PRP-1 has many potentially beneficial biological effects including immunoregulatory, hematopoietic, antimicrobial and anti-neurodegenerative properties. Here we investigated the influence of PRP-1 on staurosporine-induced apoptosis of postnatal hippocampal cells and on doxorubicin-induced bone marrow granulocyte- and monocyte apoptosis. The intention was to further characterize the effect of PRP-1 on the survival rate of neurons and in context with myelopoiesis. We demonstrate that PRP-1 significantly reduced apoptosis of postnatal hippocampal cells induced by staurosporine. The protective effect of PRP-1 against apoptotic cell death was shown to be both time- and dose-dependent. Neuroprotection was more pronounced after prolonged pretreatment of the cells with PRP-1 before the induction of apoptosis with staurosporine. The related peptide [arg(8)]vasopressin did not reveal neuroprotection. PRP-1 also significantly reduced apoptosis of bone marrow monocytes and granulocytes induced by doxorubicin. This protective effect lasted for 2-4 h and was not detectable anymore after 24 h when PRP-1 and doxorubicin were added simultaneously. Previously obtained data and results of the current studies suggested that the hypothalamic PRP-1 possibly represents an endogenous peptide whose primary functions are to regulate myelopoiesis and neuron survival as we provide evidence that PRP can differentially reduce both staurosporine- and doxorubicin-induced hippocampal and bone marrow cell apoptosis.
Galoyan
Armen A
AA
Buniatian Institute of Biochemistry of NAS RA, Yerevan, Republic of Armenia.
Krieglstein
Josef
J
Klumpp
Susanne
S
Danielian
Kristina E
KE
Galoian
Karine A
KA
Kremers
Wolfram
W
Bezirganyan
Kristina B
KB
Davtyan
Tigran K
TK
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001854:Bone Marrow Cells / Q000187:drug effects*; D004317:Doxorubicin / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology*; D055232:Proline-Rich Protein Domains; D051381:Rats; D019311:Staurosporine / Q000037:antagonists & inhibitors / Q000494:pharmacology
D010455:Peptides; D004317:Doxorubicin; D019311:Staurosporine