Human superoxide dismutase 1 attenuates quinoneimine metabolite formation from mefenamic acid

Toxicology ◽  
2021 ◽  
Vol 448 ◽  
pp. 152648
Author(s):  
Takuo Ogiso ◽  
Tatsuki Fukami ◽  
Cheng Zhongzhe ◽  
Keigo Konishi ◽  
Masataka Nakano ◽  
...  
Author(s):  
Naoki Ishii ◽  
Takujiro Homma ◽  
Jaeyong Lee ◽  
Hikaru Mitsuhashi ◽  
Ken-ichi Yamada ◽  
...  

Abstract Superoxide dismutase 1 suppresses oxidative stress within cells by decreasing the levels of superoxide anions. A dysfunction of the ovary and/or an aberrant production of sex hormones are suspected causes for infertility in superoxide dismutase 1-knockout mice. We report on attempts to rescue the infertility in female knockout mice by providing two antioxidants, ascorbic acid and/or coenzyme Q10, as supplements in the drinking water of the knockout mice after weaning and on an investigation of their reproductive ability. On the first parturition, 80% of the untreated knockout mice produced smaller litter sizes compared with wild-type mice (average 2.8 vs 7.3 pups/mouse), and supplementing with these antioxidants failed to improve these litter sizes. However, in the second parturition of the knockout mice, the parturition rate was increased from 18% to 44–75% as the result of the administration of antioxidants. While plasma levels of progesterone at 7.5 days of pregnancy were essentially the same between the wild-type and knockout mice and were not changed by the supplementation of these antioxidants, sizes of corpus luteum cells, which were smaller in the knockout mouse ovaries after the first parturition, were significantly ameliorated in the knockout mouse with the administration of the antioxidants. Moreover, the impaired vasculogenesis in uterus/placenta was also improved by ascorbic acid supplementation. We thus conclude that ascorbic acid and/or coenzyme Q10 are involved in maintaining ovarian and uterus/placenta homeostasis against insults that are augmented during pregnancy and that their use might have positive effects in terms of improving female fertility.


2018 ◽  
Vol 270 ◽  
pp. 226-236 ◽  
Author(s):  
N.V. Nukolova ◽  
A.D. Aleksashkin ◽  
T.O. Abakumova ◽  
A.Y. Morozova ◽  
I.L. Gubskiy ◽  
...  

2015 ◽  
Vol 51 (3) ◽  
pp. 584-587 ◽  
Author(s):  
E. Luchinat ◽  
A. Gianoncelli ◽  
T. Mello ◽  
A. Galli ◽  
L. Banci

Combined in-cell NMR spectroscopy, X-ray fluorescence and optical fluorescence microscopies allow describing the intracellular maturation states of human SOD1.


2010 ◽  
Vol 69 (10) ◽  
pp. 1044-1056 ◽  
Author(s):  
Shigeko Takeuchi ◽  
Noriko Fujiwara ◽  
Akemi Ido ◽  
Miki Oono ◽  
Yuki Takeuchi ◽  
...  

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Taisei Ito ◽  
Masatoshi Inden ◽  
Tomoyuki Ueda ◽  
Yuta Asaka ◽  
Hisaka Kurita ◽  
...  

AbstractAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the selective and progressive loss of motor neurons. Although many drugs have entered clinical trials, few have shown effectiveness in the treatment of ALS. Other studies have shown that the stimulation of α7 nicotinic acetylcholine receptor (nAChR) can have neuroprotective effects in some models of neurodegenerative disease, as well as prevent glutamate-induced motor neuronal death. However, the effect of α7 nAChR agonists on ALS-associated mutant copper–zinc superoxide dismutase 1 (SOD1) aggregates in motor neurons remains unclear. In the present study, we examined whether α7 nAChR activation had a neuroprotective effect against SOD1G85R-induced toxicity in a cellular model for ALS. We found that α7 nAChR activation by PNU282987, a selective agonist of α7 nAChR, exhibited significant neuroprotective effects against SOD1G85R-induced toxicity via the reduction of intracellular protein aggregates. This reduction also correlated with the activation of autophagy through the AMP-activated protein kinase (AMPK)–mammalian target of rapamycin (mTOR) signaling pathway. Furthermore, the activation of α7 nAChRs was found to increase the biogenesis of lysosomes by inducing translocation of the transcription factor EB (TFEB) into the nucleus. These results support the therapeutic potential of α7 nAChR activation in diseases that are characterized by SOD1G85R aggregates, such as ALS.


PLoS ONE ◽  
2018 ◽  
Vol 13 (11) ◽  
pp. e0206751 ◽  
Author(s):  
Keith Crosby ◽  
Anthony M. Crown ◽  
Brittany L. Roberts ◽  
Hilda Brown ◽  
Jacob I. Ayers ◽  
...  

2011 ◽  
Vol 121 (5) ◽  
pp. 623-634 ◽  
Author(s):  
Karin Forsberg ◽  
Peter M. Andersen ◽  
Stefan L. Marklund ◽  
Thomas Brännström

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