PMID- 32882929 OWN - NLM STAT- MEDLINE DCOM- 20210329 LR - 20210329 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 21 IP - 17 DP - 2020 Sep 1 TI - Cellular Signaling and Anti-Apoptotic Effects of Prolactin-Releasing Peptide and Its Analog on SH-SY5Y Cells. LID - 10.3390/ijms21176343 [doi] LID - 6343 AB - Prolactin-releasing peptide (PrRP), a natural ligand for the GPR10 receptor, is a neuropeptide with anorexigenic and antidiabetic properties. Due to its role in the regulation of food intake, PrRP is a potential drug for obesity treatment and associated type 2 diabetes mellitus (T2DM). Recently, the neuroprotective effects of lipidized PrRP analogs have been proven. In this study, we focused on the molecular mechanisms of action of natural PrRP31 and its lipidized analog palm(11)-PrRP31 in the human neuroblastoma cell line SH-SY5Y to describe their cellular signaling and possible anti-apoptotic properties. PrRP31 significantly upregulated the phosphoinositide-3 kinase-protein kinase B/Akt (PI3K-PKB/Akt) and extracellular signal-regulated kinase/cAMP response element-binding protein (ERK-CREB) signaling pathways that promote metabolic cell survival and growth. In addition, we proved via protein kinase inhibitors that activation of signaling pathways is mediated specifically by PrRP31 and its palmitoylated analog. Furthermore, the potential neuroprotective properties were studied through activation of anti-apoptotic pathways of PrRP31 and palm(11)-PrRP31 using the SH-SY5Y cell line and rat primary neuronal culture stressed with toxic methylglyoxal (MG). The results indicate increased viability of the cells treated with PrRP and palm(11)-PrRP31 and a reduced degree of apoptosis induced by MG, suggesting their potential use in the treatment of neurological disorders. FAU - Zmeskalova, Anna AU - Zmeskalova A AD - Institute of Organic Chemistry and Biochemistry, AS CR, Prague 16000, Czech Republic. AD - First Faculty of Medicine, Charles University, Prague 12108, Czech Republic. FAU - Popelova, Andrea AU - Popelova A AD - Institute of Organic Chemistry and Biochemistry, AS CR, Prague 16000, Czech Republic. FAU - Exnerova, Aneta AU - Exnerova A AD - Institute of Organic Chemistry and Biochemistry, AS CR, Prague 16000, Czech Republic. FAU - Zelezna, Blanka AU - Zelezna B AD - Institute of Organic Chemistry and Biochemistry, AS CR, Prague 16000, Czech Republic. FAU - Kunes, Jaroslav AU - Kunes J AD - Institute of Organic Chemistry and Biochemistry, AS CR, Prague 16000, Czech Republic. AD - Institute of Physiology, AS CR, Prague 14200, Czech Republic. FAU - Maletinska, Lenka AU - Maletinska L AD - Institute of Organic Chemistry and Biochemistry, AS CR, Prague 16000, Czech Republic. LA - eng GR - 20-00546S/Grantova Agentura Ceske Republiky/ GR - RVO:61388963/Akademie Ved Ceske Republiky/ PT - Journal Article DEP - 20200901 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Apoptosis Regulatory Proteins) RN - 0 (Neuropeptides) RN - 0 (Neuroprotective Agents) RN - 0 (Prolactin-Releasing Hormone) SB - IM MH - *Apoptosis MH - Apoptosis Regulatory Proteins/*metabolism MH - Humans MH - Neuroblastoma/*drug therapy/metabolism/pathology MH - Neuropeptides/chemistry/*pharmacology MH - Neuroprotective Agents/chemistry/*pharmacology MH - Prolactin-Releasing Hormone/chemistry/*pharmacology MH - Signal Transduction MH - Tumor Cells, Cultured PMC - PMC7503370 OTO - NOTNLM OT - SH-SY5Y OT - cellular signaling OT - inhibitors OT - methylglyoxal OT - neuroprotection OT - primary neuronal culture OT - prolactin-releasing peptide COIS- The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. EDAT- 2020/09/05 06:00 MHDA- 2021/03/30 06:00 PMCR- 2020/09/01 CRDT- 2020/09/05 06:00 PHST- 2020/07/10 00:00 [received] PHST- 2020/08/27 00:00 [revised] PHST- 2020/08/29 00:00 [accepted] PHST- 2020/09/05 06:00 [entrez] PHST- 2020/09/05 06:00 [pubmed] PHST- 2021/03/30 06:00 [medline] PHST- 2020/09/01 00:00 [pmc-release] AID - ijms21176343 [pii] AID - ijms-21-06343 [pii] AID - 10.3390/ijms21176343 [doi] PST - epublish SO - Int J Mol Sci. 2020 Sep 1;21(17):6343. doi: 10.3390/ijms21176343.