Novel peptides derived from neuropeptide Y prevent chemotherapy-induced bone marrow damage by regulating hematopoietic stem cell microenvironment

Min Hee Park,Bosung Baek,Hee Kyung Jin,Jae-Sung Bae

doi:10.1080/19768354.2018.1517826

Abstract

ABSTRACTChemotherapy-induced bone marrow damage is accompanied by acute nerve injury in the bone marrow (BM), resulting in sensory and autonomic neuropathy. Cisplatin, a popular chemotherapy drugs, induces the impairment of hematopoietic stem cells (HSCs) and bone marrow regeneration, leading to chronic bone marrow abnormalities. Previously, we reported the protective roles of neuropeptide Y (NPY) against cisplatin-induced bone marrow impairment. In this study, we identified novel peptides, generated from full-length NPY that rescued cisplatin-induced sensory neuropathy and HSC suppression by regulating cell survival in the BM microenvironment. One of these peptides, especially, showed a better protective property against these impairments compared to that seen in full-length NPY. Therefore, we suggest the NPY sequences most effective against the chemotherapy-induced bone marrow dysfunction that could be potentially useful as therapeutic agents for patients receiving chemotherapy.

Highlights

Chemotherapy-induced hematopoietic dysfunction is one of the severe side effects seen in patients with cancer (Noach et al 2000; Banfi et al 2001; Kemp et al 2010)
The mice treated with neuropeptide Y (NPY) (6–20) showed greater restoration of impaired hematopoietic stem cells (HSCs) than those treated with NPY (1–36)
These results indicate that NPY (6–20) is potent in preventing chemotherapy-induced HSC damage more effectively

Summary

Introduction

Chemotherapy-induced hematopoietic dysfunction is one of the severe side effects seen in patients with cancer (Noach et al 2000; Banfi et al 2001; Kemp et al 2010). Patients that have previously received chemotherapy, show dysfunction of HSCs and bone marrow regeneration, and delayed engraftment after bone marrow transplantation, leading to irreversible and chronic bone marrow failure (Mauch et al 1995; Noach et al 2000; Banfi et al 2001; Kemp et al 2010). Chemotherapy-induced nerve injury in the BM was shown to be a critical lesion impairing hematopoietic regeneration. Nerve protection as a potential therapeutic application is on the rise for prevention of long-term bone marrow injury from chemotherapy

Methods

Results

Conclusion