PM<sub>2.5</sub> Exposure-Linked Mitochondrial Dysfunction Negates SB216763-Mediated Cardio-Protection against Myocardial Ischemia–Reperfusion Injury
GSK3β is a promising target for treating various disease conditions, including myocardial ischemia–reperfusion injury (IR). This study investigated the potential of GSK3β as a novel drug for managing IR in rats exposed to PM<sub>2.5</sub> for 1 day and up to 21 days. Female Wistar rats w...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-11-01
|
| Series: | Life |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2075-1729/13/11/2234 |
| _version_ | 1797458635319672832 |
|---|---|
| author | Bhavana Sivakumar Ahmed Nadeem Mashooq Ahmad Dar Gino A. Kurian |
| author_facet | Bhavana Sivakumar Ahmed Nadeem Mashooq Ahmad Dar Gino A. Kurian |
| author_sort | Bhavana Sivakumar |
| collection | DOAJ |
| description | GSK3β is a promising target for treating various disease conditions, including myocardial ischemia–reperfusion injury (IR). This study investigated the potential of GSK3β as a novel drug for managing IR in rats exposed to PM<sub>2.5</sub> for 1 day and up to 21 days. Female Wistar rats were exposed to PM<sub>2.5</sub> at a concentration of 250 µg/m<sup>3</sup> for 3 h daily for either a single day or 21 days. After exposure, the isolated rat hearts underwent 30 min of ischemia followed by 60 min of reperfusion. GSK3β inhibition effectively reduced IR injury in rat hearts from animals exposed to PM<sub>2.5</sub> for 1 day but not in those exposed for 21 days. PM<sub>2.5</sub> exposure disrupted the redox balance in mitochondria and reduced the gene expression of antioxidants (glutaredoxin and peroxiredoxin) and NRF2, which protects against oxidative stress. PM<sub>2.5</sub> also impaired mitochondrial bioenergetics, membrane potential, and quality control, leading to mitochondrial stress. Importantly, PM<sub>2.5</sub> increased the translocation of GSK3β into mitochondria and compromised the overall mitochondrial function, particularly in the 21-day-exposed rat myocardium. The results indicate that extended exposure to PM<sub>2.5</sub> leads to oxidative stress that disrupts mitochondrial function and diminishes the effectiveness of GSK3β inhibitors in offering cardio-protection through mitochondria. |
| first_indexed | 2024-03-09T16:39:58Z |
| format | Article |
| id | doaj.art-4552a27d02ad4145a75b886eeb588c26 |
| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-09T16:39:58Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj.art-4552a27d02ad4145a75b886eeb588c262023-11-24T14:52:42ZengMDPI AGLife2075-17292023-11-011311223410.3390/life13112234PM<sub>2.5</sub> Exposure-Linked Mitochondrial Dysfunction Negates SB216763-Mediated Cardio-Protection against Myocardial Ischemia–Reperfusion InjuryBhavana Sivakumar0Ahmed Nadeem1Mashooq Ahmad Dar2Gino A. Kurian3Vascular Biology Lab, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur 613401, Tamil Nadu, IndiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaLaboratory of Preclinical Testing of Higher Standard, Nencki Institute of Experimental Biology of Polish Academy of Sciences 3, 02-093 Warsaw, PolandVascular Biology Lab, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur 613401, Tamil Nadu, IndiaGSK3β is a promising target for treating various disease conditions, including myocardial ischemia–reperfusion injury (IR). This study investigated the potential of GSK3β as a novel drug for managing IR in rats exposed to PM<sub>2.5</sub> for 1 day and up to 21 days. Female Wistar rats were exposed to PM<sub>2.5</sub> at a concentration of 250 µg/m<sup>3</sup> for 3 h daily for either a single day or 21 days. After exposure, the isolated rat hearts underwent 30 min of ischemia followed by 60 min of reperfusion. GSK3β inhibition effectively reduced IR injury in rat hearts from animals exposed to PM<sub>2.5</sub> for 1 day but not in those exposed for 21 days. PM<sub>2.5</sub> exposure disrupted the redox balance in mitochondria and reduced the gene expression of antioxidants (glutaredoxin and peroxiredoxin) and NRF2, which protects against oxidative stress. PM<sub>2.5</sub> also impaired mitochondrial bioenergetics, membrane potential, and quality control, leading to mitochondrial stress. Importantly, PM<sub>2.5</sub> increased the translocation of GSK3β into mitochondria and compromised the overall mitochondrial function, particularly in the 21-day-exposed rat myocardium. The results indicate that extended exposure to PM<sub>2.5</sub> leads to oxidative stress that disrupts mitochondrial function and diminishes the effectiveness of GSK3β inhibitors in offering cardio-protection through mitochondria.https://www.mdpi.com/2075-1729/13/11/2234PM<sub>2.5</sub>GSK 3βSB216763cardiotoxicitymyocardial ischemia–reperfusion injurymitochondria |
| spellingShingle | Bhavana Sivakumar Ahmed Nadeem Mashooq Ahmad Dar Gino A. Kurian PM<sub>2.5</sub> Exposure-Linked Mitochondrial Dysfunction Negates SB216763-Mediated Cardio-Protection against Myocardial Ischemia–Reperfusion Injury Life PM<sub>2.5</sub> GSK 3β SB216763 cardiotoxicity myocardial ischemia–reperfusion injury mitochondria |
| title | PM<sub>2.5</sub> Exposure-Linked Mitochondrial Dysfunction Negates SB216763-Mediated Cardio-Protection against Myocardial Ischemia–Reperfusion Injury |
| title_full | PM<sub>2.5</sub> Exposure-Linked Mitochondrial Dysfunction Negates SB216763-Mediated Cardio-Protection against Myocardial Ischemia–Reperfusion Injury |
| title_fullStr | PM<sub>2.5</sub> Exposure-Linked Mitochondrial Dysfunction Negates SB216763-Mediated Cardio-Protection against Myocardial Ischemia–Reperfusion Injury |
| title_full_unstemmed | PM<sub>2.5</sub> Exposure-Linked Mitochondrial Dysfunction Negates SB216763-Mediated Cardio-Protection against Myocardial Ischemia–Reperfusion Injury |
| title_short | PM<sub>2.5</sub> Exposure-Linked Mitochondrial Dysfunction Negates SB216763-Mediated Cardio-Protection against Myocardial Ischemia–Reperfusion Injury |
| title_sort | pm sub 2 5 sub exposure linked mitochondrial dysfunction negates sb216763 mediated cardio protection against myocardial ischemia reperfusion injury |
| topic | PM<sub>2.5</sub> GSK 3β SB216763 cardiotoxicity myocardial ischemia–reperfusion injury mitochondria |
| url | https://www.mdpi.com/2075-1729/13/11/2234 |
| work_keys_str_mv | AT bhavanasivakumar pmsub25subexposurelinkedmitochondrialdysfunctionnegatessb216763mediatedcardioprotectionagainstmyocardialischemiareperfusioninjury AT ahmednadeem pmsub25subexposurelinkedmitochondrialdysfunctionnegatessb216763mediatedcardioprotectionagainstmyocardialischemiareperfusioninjury AT mashooqahmaddar pmsub25subexposurelinkedmitochondrialdysfunctionnegatessb216763mediatedcardioprotectionagainstmyocardialischemiareperfusioninjury AT ginoakurian pmsub25subexposurelinkedmitochondrialdysfunctionnegatessb216763mediatedcardioprotectionagainstmyocardialischemiareperfusioninjury |