title: Insights on a new path of pre-mitochondrial apoptosis regulation by a glycosaminoglycan mimetic.
abstract: Lysosomal cathepsins have recently been reported to play crucial roles in the regulation of the mitochondrial death cascade by an unclear mechanism leading to mitochondrial membrane permeabilization. Glycosaminoglycans (GAG) are a family of ionic polysaccharides present at the lysosomal compartment and shown to inhibit lysosomal cathepsin activities. The implication of this family of polysaccharides in the regulation of the pre-mitochondrial death cascade has still not been considered. Here, we demonstrate in a model of skin fibroblasts submitted to oxidative stress that a GAG-mimetic protects the lysosome from membrane disruption, reduces intracellular ROS levels, and inhibits mitochondrial membrane potential collapse, cytochrome c release and caspases-9 and -3 activations without affecting the extrinsic pathway of apoptosis. Heparan sulfate and chondroitin sulfate, but not heparin, showed also protecting effects when assessing key points of the intrinsic pathway of apoptosis. We suggest the existence of molecular links between endogenous GAGs and the regulation of apoptosis.
authors.affiliation: Laboratoire CRRET CNRS UMR 7149, Université Paris-Est, 94010 Créteil, France.
authors.forename: X-L
authors.initials: XL
authors.lastname: Yue
authors.forename: S
authors.initials: S
authors.lastname: Lehri
authors.forename: P
authors.initials: P
authors.lastname: Li
authors.forename: V
authors.initials: V
authors.lastname: Barbier-Chassefière
authors.forename: E
authors.initials: E
authors.lastname: Petit
authors.forename: Q-F
authors.initials: QF
authors.lastname: Huang
authors.forename: P
authors.initials: P
authors.lastname: Albanese
authors.forename: D
authors.initials: D
authors.lastname: Barritault
authors.forename: J-P
authors.initials: JP
authors.lastname: Caruelle
authors.forename: D
authors.initials: D
authors.lastname: Papy-Garcia
authors.forename: C
authors.initials: C
authors.lastname: Morin
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002402:Cathepsin D / Q000378:metabolism; D002478:Cells, Cultured; D002809:Chondroitin Sulfates / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006025:Glycosaminoglycans / Q000494:pharmacology*; D006497:Heparan Sulfate / Q000494:pharmacology; D008247:Lysosomes / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D053148:Caspase 3; D053453:Caspase 9; D002402:Cathepsin D; D002809:Chondroitin Sulfates; D045304:Cytochromes c; D006025:Glycosaminoglycans; D006497:Heparan Sulfate; D017382:Reactive Oxygen Species; C533322:OTR4120