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.
FengLin Wang  1 ,  Yan Zeng  2 ,  Xian Liu  3 ,  JiaJun Cao  4 ,  ShengNan Kang  5 ,  WuShuang Zhou  6 ,  XiaoYing Chen  7 ,  JingLun Liu  8 ,  Dan Zhang  9
Affiliations
  • 1. Department of Emergency, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, PR China. Electronic address: [email protected].
  • 2. Department of Emergency, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, PR China; Intensive Care Unit, Chongqing University Central Hospital, Chongqing, 400016, PR China. Electronic address: [email protected].
  • 3. Department of Emergency, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, PR China. Electronic address: [email protected].
  • 4. Department of Emergency, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, PR China. Electronic address: [email protected].
  • 5. Department of Emergency, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, PR China. Electronic address: [email protected].
  • 6. Department of Emergency, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, PR China. Electronic address: [email protected].
  • 7. Department of Surgical Care Unit, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, PR China. Electronic address: [email protected].
  • 8. Department of Emergency, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, PR China. Electronic address: [email protected].
  • 9. Department of Emergency, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, PR China. Electronic address: [email protected].
PMID: 35339012 DOI: 10.1016/j.bbrc.2022.03.046
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.
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