Post-Treatment with Amorfrutin B Evokes PPARγ-Mediated Neuroprotection against Hypoxia and Ischemia
| Autor: | Karolina Przepiórska, Bernadeta A Pietrzak, Agnieszka Wnuk, Małgorzata Kajta |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Peroxisome proliferator-activated receptor gamma DNA damage QH301-705.5 Medicine (miscellaneous) ischemia Pharmacology Neuroprotection General Biochemistry Genetics and Molecular Biology Article selective PPARγ modulator 03 medical and health sciences 0302 clinical medicine medicine Gene silencing Biology (General) Receptor perinatal asphyxia Messenger RNA Chemistry hypoxia Hypoxia (medical) stroke post-treatment 030104 developmental biology DNA methylation neuroprotection medicine.symptom 030217 neurology & neurosurgery |
| Zdroj: | Biomedicines, Vol 9, Iss 854, p 854 (2021) Biomedicines Volume 9 Issue 8 |
| ISSN: | 2227-9059 |
| Popis: | In this study, we demonstrate for the first time that amorfrutin B, a selective modulator of peroxisome proliferator-activated receptor gamma—PPARγ, can protect brain neurons from hypoxia- and ischemia-induced degeneration when applied at 6 h post-treatment in primary cultures. The neuroprotective effect of amorfrutin B suggests that it promotes mitochondrial integrity and is capable of inhibiting reactive oxygen species—ROS activity and ROS-mediated DNA damage. PPARγ antagonist and Pparg mRNA silencing abolished the neuroprotective effect of amorfrutin B, which points to agonistic action of the compound on the respective receptor. Interestingly, amorfrutin B stimulated the methylation of the Pparg gene, both during hypoxia and ischemia. Amorfrutin B also increased the protein level of PPARγ during hypoxia but decreased the mRNA and protein levels of PPARγ during ischemia. Under ischemic conditions, amorfrutin B-evoked hypermethylation of the Pparg gene is in line with the decrease in the mRNA and protein expression of PPARγ. However, under hypoxic conditions, amorfrutin B-dependent hypermethylation of the Pparg gene does not explain the amorfrutin B-dependent increase in receptor protein expression, which suggests other regulatory mechanisms. Other epigenetic parameters, such as HAT and/or sirtuins activities, were affected by amorfrutin B under hypoxic and ischemic conditions. These properties position the compound among the most promising anti-stroke and wide-window therapeutics. |
| Databáze: | OpenAIRE |
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