Galectin-1 sensitizes resting human T lymphocytes to Fas (CD95)-mediated cell death via mitochondrial hyperpolarization, budding, and fission

J Biol Chem. 2005 Feb 25;280(8):6969-85. doi: 10.1074/jbc.M409752200. Epub 2004 Nov 19.

Abstract

Galectins have emerged as a novel family of immunoregulatory proteins implicated in T cell homeostasis. Recent studies showed that galectin-1 (Gal-1) plays a key role in tumor-immune escape by killing antitumor effector T cells. Here we found that Gal-1 sensitizes human resting T cells to Fas (CD95)/caspase-8-mediated cell death. Furthermore, this protein triggers an apoptotic program involving an increase of mitochondrial membrane potential and participation of the ceramide pathway. In addition, Gal-1 induces mitochondrial coalescence, budding, and fission accompanied by an increase and/or redistribution of fission-associated molecules h-Fis and DRP-1. Importantly, these changes are detected in both resting and activated human T cells, suggesting that Gal-1-induced cell death might become an excellent model to analyze the morphogenetic changes of mitochondria during the execution of cell death. This is the first association among Gal-1, Fas/Fas ligand-mediated cell death, and the mitochondrial pathway, providing a rational basis for the immunoregulatory properties of Gal-1 in experimental models of chronic inflammation and cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis Regulatory Proteins
  • Apoptosis*
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Caspase 8
  • Caspases
  • Cells, Cultured
  • Death-Associated Protein Kinases
  • Galectin 1 / analogs & derivatives*
  • Galectin 1 / pharmacology*
  • Humans
  • Intracellular Membranes / pathology
  • Membrane Potentials
  • Membrane Proteins
  • Mitochondria / drug effects
  • Mitochondria / pathology*
  • Mitochondria / physiology
  • Mitochondrial Proteins / metabolism
  • Protein-Serine-Threonine Kinases / metabolism
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects*
  • Tumor Escape*
  • fas Receptor / physiology*

Substances

  • Apoptosis Regulatory Proteins
  • FIS1 protein, human
  • Galectin 1
  • LGALS1 protein, human
  • Membrane Proteins
  • Mitochondrial Proteins
  • fas Receptor
  • Death-Associated Protein Kinases
  • Protein-Serine-Threonine Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • CASP8 protein, human
  • Caspase 8
  • Caspases