Catalase and estradiol inhibit mitochondrial protein S-glutathionylation.
Regulation and downstream effects of mitochondrial protein S-glutathionylation in response to oxidative stress are poorly understood. The study aim was to determine whether anti-oxidants such as catalase and estradiol alter mitochondrial protein S-glutathionylation and in turn affect apoptosis following ultraviolet B (UV-B) light irradiation. HeLa cells were transduced with increasing amounts of adenovirus encoding catalase (Ad-Cat) and β-galactosidase (Ad-Lac Z) or pre-incubated with estradiol before induction of apoptosis by UV-B light exposure. Inhibition of mitochondrial protein S-glutathionylation was assessed using autoantibodies specific for the non-S-glutathionylated form of PDC-E2. The percentage of apoptotic cells following UV-B irradiation were not significantly different between mock cells (cells with no virus infection) and Ad-Cat and Ad-Lac Z infected cells at all viral doses (all p > 0.050). Autoantibody staining of non-S-glutathionylated PDC-E2 in apoptotic cells was three times greater in only Ad-Cat infected cells compared to only Ad-Lac Z infected cells (81.3 ± 16.7 vs 26 ± 7.2 %, respectively, p = 0.030). Similarly estradiol treatment (33 and 100 nM) also significantly increased PDC-E2 staining in apoptotic cells compared to non-treated cells (both p < 0.010). The percentage of apoptotic cells was not significantly different with any of the estradiol concentrations (all p > 0.100). The observed procaspase 12 cleavage following UV-B irradiation suggests that a mitochondrial-independent apoptotic pathway was activated. In conclusion, following an apoptotic stimulus, estradiol may inhibit mitochondrial protein S-glutathionylation without inhibiting apoptosis. This effect may play a role in ninefold greater prevalence of autoantibodies against PDC-E2 in women with primary biliary cirrhosis.
Department of Medicine, The Mount Sinai School of Medicine, New York, NY 10029, USA.
Bin
B
Hu
Jorge
J
Allina
Jingxiang
J
Bai
Vivek
V
Kesar
Joseph A
JA
Odin
D000975:Antioxidants / Q000494:pharmacology / Q000502:physiology*; D017209:Apoptosis; D002374:Catalase / Q000378:metabolism / Q000502:physiology*; D051047:Dihydrolipoyllysine-Residue Acetyltransferase / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology / Q000502:physiology*; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D024101:Mitochondrial Proteins / Q000378:metabolism*; D018384:Oxidative Stress
D000975:Antioxidants; D024101:Mitochondrial Proteins; D004958:Estradiol; D002374:Catalase; D051047:Dihydrolipoyllysine-Residue Acetyltransferase; D005978:Glutathione