Altered Galectin Glycosylation: Potential Factor for the Diagnostics and Therapeutics of Various Cardiovascular and Neurological Disorders

Abstract

Galectins are β-galactoside binding mammalian proteins characterized by the presence of a conserved carbohydrate recognition domain, expressed in almost all taxa of living organisms and involved in broad range of significant biological and physiological functions. Previously, we reported the purification and extensive characterization of galectin-1 from goat (Capra hircus) heart. Interestingly, the purified protein was found to have significant level of glycosylation. This intrigued us to evaluate the involvement of glycosylation in relation to protein's structural and functional integrity in its purified form. In the present study, an extensive comparative physicochemical characterization has been performed between the glycosylated and deglycosylated form of the purified protein. Deglycosylation resulted in an enhanced fluorescence quenching and marked reduction in pH and thermal stability of the purified galectin. Exposure to various biologically active chemicals showed significant differences in the properties and stability profile, causing significant deviations from its regular secondary structure in the deglycosylated form. These results clearly indicated enhanced structural and functional stabilization in the glycosylated galectin. The data revealed herein adds a vital facet demonstrating the significance of galectin expression and glycosylation in causation, progression, and possible therapeutics of associated clinical disorders. Our approach also allowed us to define some key interactions between the purified galectin and carbohydrate ligands that could well serve as an important landmark for designing new drug protocols for various cardiovascular and neurological disorders.

Investigation of Gal-3 Expression Pattern in Serum and Cerebrospinal Fluid of Patients Suffering From Neurodegenerative Disorders

“…Gal-3 functional roles have been reported in CNS ( Bresalier et al, 1997 ; Reichert and Rotshenker, 1999 ). Gal-3 inductions are evident in various pathological processes of brain diseases such as prion diseases, ALS, AD, ischemic brain lesions, and PD ( Jin et al, 2007 ; Lerman et al, 2012 ; Ashraf et al, 2015 ). The possible physiological role of Gal-3 in AD and ALS can be investigated by exploring its already established biological functions like their role in inflammation and apoptosis (extracellular Gal-3 being proapoptotic, and intracellular Gal-3 being anti-apoptotic) ( Yu et al, 2002 ; Nangia-Makker et al, 2007 ; Henderson and Sethi, 2009 ; Ashraf et al, 2010a ; Siwicki et al, 2016 ).…”

The apoptotic effect of resveratrol in ovarian cancer cells is associated with downregulation of galectin‐3 and stimulating miR‐424‐3p transcription

“…Currently, it is well accepted that GALs can regulate numerous cell function such as inflammation and survival by regulating various cell signaling pathways (Ashraf et al, ; Ashraf, Perveen, Tabrez, et al, ; Ashraf, Perveen, Zaidi, et al, ). GAL‐3 was shown to stimulate cell survival through activation of Akt and NF‐κB signaling and plays a crucial role in promoting tumorigenesis and drug resistance of various tumors including OC (Mirandola, Yu, et al, ).…”

“…On the other hand, available literature reports relevant roles of galectins (GALs) in modulation of acute inflammatory response and protection against several disorders (Ashraf, Mahmoud, & Tabrez, ; Ashraf, Perveen, Tabrez, et al, ; Ashraf, Perveen, Zaidi, et al, ). Galectin‐3 (GAL‐3) (coded by LGALS3 gene) is an S‐type lectin that binds β‐galactose‐containing glycoconjugates and is highly expressed on the surface, nuclei, and cytoplasm of the cells and is abundantly found in the circulation (Mirandola, Yu, et al, ).…”

High-glucose environment induced intracellular O-GlcNAc glycosylation and reduced galectin-7 expression in keratinocytes: Implications on impaired diabetic wound healing

“…Two intracellular enzymes, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), mediate addition and removal, respectively, of O-GlcNAc glycosylation from intracellular protein substrates [27]. Ashraf et al reported that goat heart Gal-1 with GlcNAc glycosylation had protection against damage and denaturation by biologically active chemicals as compare to the deglycosylated form [28]. In this study, Gal-7 expression reduction was not only observed at protein levels but also at mRNA levels after exposing keratinocytes to high-glucose environment.…”