RGS12 is a target of penehyclidine hydrochloride that enhances oxidative stress and ferroptosis in a model of myocardial ischemia/reperfusion injury by inhibiting the Nrf2 pathway DOI Creative Commons

Congna Zi,

Yulei Wei, Ying Zhu

et al.

International Journal of Molecular Medicine, Journal Year: 2025, Volume and Issue: 55(3)

Published: Jan. 24, 2025

Regulator of G‑protein signaling 12 (RGS12) is a regulatory factor that involved in various physiological processes. However, the role RGS12 myocardial ischemia/reperfusion injury (MIRI) currently remains unclear. The present study established mouse model MIRI by ligating left main coronary artery followed reperfusion. In addition, HL‑1 cells were cultured hypoxic and serum‑free medium, reoxygenation to establish an in vitro cell hypoxia/reoxygenation (H/R). Adenoviruses targeting subsequently used either overexpress or silence expression. was highly expressed both tissues mice with subjected H/R. results from experiments demonstrated knockdown reduced oxidative stress under pathological environment, as indicated decreased reactive oxygen species (ROS) levels malondialdehyde activity increased activities superoxide dismutase catalase. Furthermore, underwent H/R stimulation exhibited ferroptosis, whereas reversed these changes. These showed post‑RGS12 silencing Fe2+ lipid ROS decreased, expression glutathione peroxidase 4 cystine transporter solute carrier family 7 member 11 mitochondrial structure improved preventing loss crest. Mechanistically, nuclear erythroid 2‑related 2 (Nrf2) pathway anti‑ferroptosis anti‑oxidative capacities activated knockdown. Conversely, overexpression exerted opposite effects vivo vitro. Notably, it penehyclidine hydrochloride (PHC), known block process, vivo vitro, inhibited therapeutic PHC on MIRI. conclusion, RGS12, target PHC, potentially enhanced progression promoting this effect may involve regulation Nrf2 pathway.

Language: Английский

Iron accumulation and lipid peroxidation: implication of ferroptosis in diabetic cardiomyopathy DOI Creative Commons
Xuehua Yan, Yang Xie, Hongbing Liu

et al.

Diabetology & Metabolic Syndrome, Journal Year: 2023, Volume and Issue: 15(1)

Published: July 19, 2023

Diabetic cardiomyopathy (DC) is a serious heart disease caused by diabetes. It unrelated to hypertension and coronary artery can lead insufficiency, failure even death. Currently, the pathogenesis of DC unclear, clinical intervention mainly symptomatic therapy lacks effective objectives. Iron overdose mediated cell death, also known as ferroptosis, widely present in physiological pathological processes diabetes DC. key trace element human body, regulating metabolism glucose lipids, oxidative stress inflammation, other biological processes. Excessive iron accumulation imbalance antioxidant system activate aggravate such excessive autophagy mitochondrial dysfunction, resulting chain reaction accelerating myocardial microvascular damage. In-depth understanding mechanisms ferroptosis cardiovascular vessels help improve management. Therefore, this review, we summarize relationship between DC, well potential targets, discuss analyze limitations future development prospects these targets.

Language: Английский

Citations

12
Non-apoptotic cell death programs in cervical cancer with an emphasis on ferroptosis DOI
Mohammad Samare‐Najaf, Ali Samareh, Amir Savardashtaki

et al.

Critical Reviews in Oncology/Hematology, Journal Year: 2023, Volume and Issue: 194, P. 104249 - 104249

Published: Dec. 23, 2023

Language: Английский

Citations

11
Exploring the molecular biology of ischemic cardiomyopathy based on ferroptosis‑related genes DOI Open Access

Shi-Tao Zhao,

Zhi-Cong Qiu,

Rui-Yuan Zeng

et al.

Experimental and Therapeutic Medicine, Journal Year: 2024, Volume and Issue: 27(5)

Published: March 22, 2024

Ischemic cardiomyopathy (ICM) is a serious cardiac disease with very high mortality rate worldwide, which causes myocardial ischemia and hypoxia as the main damage. Further understanding of underlying pathological processes cardiomyocyte injury key to development cardioprotective strategies. Ferroptosis an iron‑dependent form regulated cell death characterized by accumulation lipid hydroperoxides lethal levels, resulting in oxidative damage membrane. The current role regulation ferroptosis ICM still limited, especially absence evidence from large‑scale transcriptomic data. Through comprehensive bioinformatics analysis human transcriptome data obtained Gene Expression Omnibus database, present study identified differentially expressed ferroptosis‑related genes (DEFRGs) ICM. Subsequently, their potential biological mechanisms cross‑talk were analyzed, hub constructing protein‑protein interaction networks. features such reactive oxygen species generation, changes marker proteins, iron ion aggregation oxidation, H9c2 anoxic reoxygenation model. Finally, diagnostic ability Gap junction alpha‑1 (GJA1), Solute carrier family 40 member 1 (SLC40A1), Alpha‑synuclein (SNCA) through receiver operating characteristic curves expression DEFRGs was verified in vitro Furthermore, drugs (retinoic acid) that could regulate predicted based on DEFRGs. article presents new insights into ICM, investigating regulatory process advocating for novel therapeutic target transcriptome.

Language: Английский

Citations

4
Ferroptosis: First evidence in premature duck ovary induced by polyvinyl chloride microplastics DOI

Waseem Ali,

Yan Chen,

Muhammad Ghiasuddin Shah

et al.

The Science of The Total Environment, Journal Year: 2024, Volume and Issue: 933, P. 173032 - 173032

Published: May 9, 2024

Language: Английский

Citations

4
RGS12 is a target of penehyclidine hydrochloride that enhances oxidative stress and ferroptosis in a model of myocardial ischemia/reperfusion injury by inhibiting the Nrf2 pathway DOI Creative Commons

Congna Zi,

Yulei Wei, Ying Zhu

et al.

International Journal of Molecular Medicine, Journal Year: 2025, Volume and Issue: 55(3)

Published: Jan. 24, 2025

Regulator of G‑protein signaling 12 (RGS12) is a regulatory factor that involved in various physiological processes. However, the role RGS12 myocardial ischemia/reperfusion injury (MIRI) currently remains unclear. The present study established mouse model MIRI by ligating left main coronary artery followed reperfusion. In addition, HL‑1 cells were cultured hypoxic and serum‑free medium, reoxygenation to establish an in vitro cell hypoxia/reoxygenation (H/R). Adenoviruses targeting subsequently used either overexpress or silence expression. was highly expressed both tissues mice with subjected H/R. results from experiments demonstrated knockdown reduced oxidative stress under pathological environment, as indicated decreased reactive oxygen species (ROS) levels malondialdehyde activity increased activities superoxide dismutase catalase. Furthermore, underwent H/R stimulation exhibited ferroptosis, whereas reversed these changes. These showed post‑RGS12 silencing Fe2+ lipid ROS decreased, expression glutathione peroxidase 4 cystine transporter solute carrier family 7 member 11 mitochondrial structure improved preventing loss crest. Mechanistically, nuclear erythroid 2‑related 2 (Nrf2) pathway anti‑ferroptosis anti‑oxidative capacities activated knockdown. Conversely, overexpression exerted opposite effects vivo vitro. Notably, it penehyclidine hydrochloride (PHC), known block process, vivo vitro, inhibited therapeutic PHC on MIRI. conclusion, RGS12, target PHC, potentially enhanced progression promoting this effect may involve regulation Nrf2 pathway.

Language: Английский

Citations

0