Mitochondria hyperpolarization is an early event in oxidized low-density lipoprotein-induced apoptosis in Caco-2 intestinal cells.
We investigated the mechanisms underlying the pro-apoptotic activity exerted by oxidized low-density lipoproteins (oxLDL) in Caco-2 intestinal cells, a cell line which retains many morphological and enzymatic features typical of normal human enterocytes. We found that: (i) oxLDL induced mitochondrial-mediated apoptosis by provoking first an increase in mitochondrial membrane potential, followed, later, by the typical apoptosis-associated depolarization (type II apoptosis); accordingly, (ii) caspase-9 inhibition significantly hindered apoptosis while caspase-8 inhibition did not; and finally (iii) dietary phenolic antioxidizing compounds exerted a significant protective antiapoptotic activity. These results point to mitochondrial hyperpolarization as 'sensitizing feature' in apoptotic proneness of Caco-2 intestinal cells to oxLDL exposure.
Department of Metabolism and Biochemical Pathology, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy. clagiovn@iss.it
Claudio
C
Giovannini
Paola
P
Matarrese
Beatrice
B
Scazzocchio
Massimo
M
Sanchez
Roberta
R
Masella
Walter
W
Malorni
D017209:Apoptosis / Q000502:physiology*; D018938:Caco-2 Cells / Q000187:drug effects* / Q000502:physiology; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008564:Membrane Potentials / Q000502:physiology; D008928:Mitochondria / Q000502:physiology*; D008954:Models, Biological; D010084:Oxidation-Reduction
D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases