Chromogranin A-derived peptide CGA47-66 protects against septic brain injury by reducing blood-brain barrier damage through the PI3K/AKT pathway

Biochem Biophys Res Commun. 2022 May 21:605:162-170. doi: 10.1016/j.bbrc.2022.03.046. Epub 2022 Mar 18.

Abstract

CGA47-66 (Chromofungin, CHR), is a peptide derived from the N-terminus of chromogranin A (CgA), has been proven to inhibit the lipopolysaccharide (LPS)-induced brain injury. However, the underlying mechanism is still unknown. We found that CGA47-66 exerted a protective effect on cognitive impairment by inhibiting the destruction of the blood-brain barrier (BBB) in the LPS-induced sepsis mice model. In addition, the hCMEC/D3 cell line was used to establish an in vitro BBB model. Under LPS stimulation, CGA47-66 could significantly alleviate the hyperpermeability of the BBB, the destruction of tight junction proteins, and the rearrangement of F-actin. To investigate the underlying mechanism, we used LY294002, a PI3K inhibitor, which partially reduced the protective effect of CGA47-66 on the integrity of BBB. Indicating that the PI3K/AKT pathway plays a vital role in the brain-protective function of CGA47-66, which might be a potential therapeutic target for septic brain injury.

Keywords: Blood-brain barrier; CGA(47-66); Cognitive impairment; PI3K/AKT; Septic brain injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood-Brain Barrier* / metabolism
  • Brain / metabolism
  • Brain Injuries* / drug therapy
  • Brain Injuries* / metabolism
  • Brain Injuries* / prevention & control
  • Chromogranin A / metabolism
  • Chromogranin A / pharmacology
  • Lipopolysaccharides / pharmacology
  • Mice
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism

Substances

  • Chromogranin A
  • Lipopolysaccharides
  • Proto-Oncogene Proteins c-akt