Protein 4.1 family and ion channel proteins interact to regulate the process of heart failure in rats

Acta Histochem. 2021 Sep;123(6):151748. doi: 10.1016/j.acthis.2021.151748. Epub 2021 Jul 13.

Abstract

Heart failure (HF) is a major cause of death in cardiovascular diseases worldwide, and its molecular mechanisms and effective prevention strategies remain to be further studied. The myocardial cytoskeleton plays a pivotal role in many heart diseases. However, little is known about the function of the membrane cytoskeleton 4.1 protein family and related regulatory mechanisms in the pathogenesis of HF. In this study, we detected the localization and expression of the protein 4.1 family and ion channel proteins in a rat HF model induced by doxorubicin (DOX), and studied the interactions between them. Our results showed that compared with the control group, the HF group displayed an increased expression level of protein 4.1R and decreased levels of protein 4.1 G and 4.1 N. The Nav1.5 protein levels were significantly increased, while the SERCA2a and Cav1.2 protein levels were significantly decreased in the HF group. Furthermore, there is co-localization and interaction between protein 4.1R and Nav1.5, protein 4.1 G and SERCA2a, protein 4.1 N and Cav1.2, respectively. Taken together, the results indicated that the protein 4.1 family might be involved in the occurrence and development of HF through its interaction with ion channel proteins, suggesting that 4.1 proteins may serve as a novel therapeutic target for HF.

Keywords: 4.1 Proteins; Heart failure; Ion channel proteins; Myocardial cytoskeleton; Protein Interaction.

MeSH terms

  • Animals
  • Calcium Channels, L-Type / genetics
  • Calcium Channels, L-Type / metabolism*
  • Heart Failure / genetics
  • Heart Failure / metabolism*
  • Male
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism*
  • Myocardium / metabolism*
  • NAV1.5 Voltage-Gated Sodium Channel / genetics
  • NAV1.5 Voltage-Gated Sodium Channel / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / genetics
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / metabolism*

Substances

  • Cacna1c protein, rat
  • Calcium Channels, L-Type
  • Epb41l1 protein, rat
  • Microfilament Proteins
  • NAV1.5 Voltage-Gated Sodium Channel
  • Scn5a protein, rat
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases