Novel humanin analogs confer neuroprotection and myoprotection to neuronal and myoblast cell cultures exposed to ischemia-like and doxorubicin-induced cell death insults

Chaim Gilon, Agata Gitlin-Domagalska, Adi Lahiani, Shiran Yehoshua-Alshanski, Adi Shumacher-Klinger, Dan Gilon, Mahmoud Taha, Israel Sekler, Amnon Hoffman, Philip Lazarovici*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Humanin (HN) is a 24-amino acid mitochondrial-derived peptide, best known for its ability to protect neurons from damage caused by ischemic stroke and neurodegenerative insults and cardiomyocytes from myocardial infarction or doxorubicin (Dox)-induced cardiotoxicity. This study examines the neuroprotective and myoprotective effects of HN novel synthetic analogs HUJInin and c(D-Ser14-HN), prepared by solid-phase peptide synthesis. The cellular models employed were oxygen-glucose-deprivation (OGD) followed by reoxygenation (R)-induced neurotoxicity in PC12 and SH-SY5Y neuronal cell cultures and Dox-induced cardiotoxicity in H9c2 and C2C12 myoblast cell cultures, respectively. Necrotic and apoptotic cell death was measured by LDH release and caspase-3 activity. Erk 1/2 and AKT phosphorylations were examined by western blotting. Mitochondrial calcium and mitochondrial membrane potential were measured using the fluorescent dye tetramethylrhodamine-methyl ester. It was found that HUJInin and c(D-Ser14-HN) conferred significant dose-dependent neuroprotection, a phenomenon related to attenuation of OGD insult-induced Erk 1/2 phosphorylation, stimulation of AKT phosphorylation and improvement of mitochondrial functions. These peptides also conferred myoprotective effect towards Dox-induced apo-necrotic cell death insults. HUJInin and c(D-Ser14-HN) synthetic analogs may provide new lead compounds for the development of a potential candidate drug for stroke treatment and/or Dox-induced cardiotoxicity therapy in cancer patients.

Original languageAmerican English
Article number170399
JournalPeptides
Volume134
DOIs
StatePublished - Dec 2020

Bibliographical note

Publisher Copyright:
© 2020

Keywords

  • AKTc(D-Ser14)HN
  • Apoptosis
  • Doxorubicin
  • Erk1/2
  • HUJInin
  • Humanin
  • Mitochondria
  • Myoprotection
  • Necrosis
  • Neuroprotection
  • Peptides
  • Synthetic analog

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