The effect of aging on the response of isolated hepatocytes to hydrogen peroxide and tert-butyl hydroperoxide.
Aging is associated with increased susceptibility to oxidative stress. To study this in the liver and to elucidate underlying mechanisms, hepatocytes from young (4-6 months) and old (24-26 months) rats were exposed to two oxidants, hydrogen peroxide and tert-butyl hydroperoxide. ATP content and mitochondrial activity were lower in old hepatocytes and decreased further with oxidative stress. Expression of Cu/Zn superoxide dismutase, Mn superoxide dismutase and catalase was not substantially influenced by oxidative stress in young and old hepatocytes, whereas glutathione peroxidase 1 expression was markedly increased only in young hepatocytes. Oxidative stress in young hepatocytes led to increased expression of apoE and movement of apoE to the early endosomes. In old hepatocytes, oxidative stress did not increase apoE expression and apoE was co-localized with early endosomes under control conditions. The results show that old age is associated with impaired hepatocyte responses of mitochondria, ATP, glutathione peroxidase 1 and apoE to oxidative stress.
Sabaretnam
Tharani
T
ANZAC Research Institute, University of Sydney, Australia.
Kritharides
Leonard
L
O'Reilly
Jennifer N
JN
Le Couteur
David G
DG
D000255:Adenosine Triphosphate / Q000378:metabolism; D000375:Aging / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001057:Apolipoproteins E / Q000096:biosynthesis / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D016877:Oxidants / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000378:metabolism; D020122:tert-Butylhydroperoxide / Q000633:toxicity*
D000975:Antioxidants; D001057:Apolipoproteins E; D016877:Oxidants; D000255:Adenosine Triphosphate; D020122:tert-Butylhydroperoxide; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase