Galectin‐3 overexpression protects from cell damage and death by influencing mitochondrial homeostasis

Abstract

Galectins are a family of proteins involved in several cell processes, including their survival and death. Galectin-3 has in particular been described as an anti-apoptotic molecule entangled with a number of subcellular activities including anoikis resistance. In this work we partially address the mechanisms underlying this activity pointing at two key factors in injury progression: the alteration of mitochondrial membrane potential and the formation of reactive oxygen species. Overexpression of galectin-3 appears in fact to exert a protective effect towards both these events. On the basis of these data, we propose a reappraisal of the role of galectin-3 as a regulator of mitochondrial homeostasis.z 2000 Federation of European Biochemical Societies.

Inhibition of N-(4-hydroxyphenyl)retinamide-Induced Apoptosis in Breast Cancer Cells by Galectin-3

“…Although it is not clear how galectin-3 suppresses ROS generation by 4HPR, it is noteworthy that in BT549 cells, galectin-3 translocates to the perinuclear mitochondrial membranes and inhibits cytochrome c release following a variety of apoptotic stimuli 43 and overexpression of galecin-3 in other breast carcinoma cells also decreased ROS production following TNFα treatment. 44 These results suggest that tumors in which galectin-3 expression increases during tumor progression may become resistant to 4HPR and other proapoptotic agents or signals that act via an increase in ROS production and that this resistance may impact on treatment outcomes. Therefore, targeting galectin-3 may enhance response to therapy by certain agents.…”

Dual activities of galectin-3 in human prostate cancer: tumor suppression of nuclear galectin-3 vs tumor promotion of cytoplasmic galectin-3

“…In BT-549 breast cancer cells, Gal-3 inhibits the intrinsic apoptotic pathway (Akahani et al, 1997;Kim et al, 1999;Matarrese et al, 2000a;Moon et al, 2001) but not the extrinsic pathway (unpublished data cited in Moon et al, 2001). However, Gal-3 counteracts TNF-ainduced apoptosis, involving the extrinsic pathway, in another breast cancer cell line (Matarrese et al, 2000b). In LNCaP cells, cytoplasmic Gal-3 inhibits both intrinsic (actinomycin D or X-ray irradiation) and extrinsic (TNF-a) apoptotic pathways.…”

Intra-articular lentivirus-mediated delivery of galectin-3 shRNA and galectin-1 gene ameliorates collagen-induced arthritis

“…25 Recent studies suggest that endogenous galectin-3 brings about apoptosis resistance by engaging apoptosis regulation pathways or modulating homeostasis of mitochondria. [25][26][27] Galectin-3 is secreted by cultured cells and detectable in extracellular fluid under inflammatory conditions and, through its multivalent lectin activity, galctin-3 induces interleukin-2 production by T cells. 28 Galectin-3 binds to the extracellular matrix in the carbohydrate-dependent manner and promotes cell adhesion by activating adhesion molecules.…”