Elabela alleviates cuproptosis and vascular calcification in vitaminD3- overloaded mice via regulation of the PPAR-γ /FDX1 signaling DOI Creative Commons

Rui-Qiang Qi,

Yufei Chen,

Jing Cheng

et al.

Molecular Medicine, Journal Year: 2024, Volume and Issue: 30(1)

Published: Nov. 20, 2024

Abstract Background Vascular calcification is a crucial pathophysiological process associated with age-related cardiovascular diseases. Elabela, recently identified peptide, has emerged as significant player in the regulation of function and homeostasis. However, effects underlying mechanisms Elabela on vascular remain largely unexplored. Methods In-vivo calcifications C57BL/6J mice (8-week-old) young or aged (72-week-old) SD rats were injected vitamin D3 (VitD3) saline, respectively. Furthermore, VitD3-overloaded received (1 mg/kg/d), peroxisome proliferators-activated receptor-γ (PPAR-γ) activator Rosiglitazone (5 mg/kg/d) copper-ionophore Elesclomol (20 As for in-vitro studies, primary rat smooth muscle cells (VSMCs) isolated from aortas cultured explore role mechanism calcification. Results There marked increases FDX1 Slc31a1 levels both VSMCs during calcification, coinciding rise copper decrease levels. Alizarin red von-Kossa staining indicated that administration effectively hindered progression cuproptosis arterial rings models. Moreover, significantly suppressed osteogenic differentiation calcium deposition strikingly reversed high phosphate-induced augmentation expression, DLAT aggregation well intracellular ion More importantly, exhibited remarkable abilities to prevent mitochondrial dysfunctions by maintaining membrane potential, inhibiting division, reducing ROS production increasing ATP Interestingly, mitigated cellular senescence pro-inflammatory cytokines including IL-1α, IL-1β, IL-6, IL-18 TNF-α, upregulated protein PPAR-γ mice. Administrating inhibitor GW9662 blocking efflux abolished protective effect enhancing FDX1, Slc31a1, Runx2, BMP2. Conclusion plays protecting against activating /FDX1 signaling. supplementation suppression serve effective therapeutic approaches managing related disorders.

Language: Английский

Targeting ion homeostasis in metabolic diseases: molecular mechanisms and targeted therapies DOI Creative Commons
Yanjiao Zhang,

Kaile Ma,

Xinyi Fang

et al.

Pharmacological Research, Journal Year: 2025, Volume and Issue: 212, P. 107579 - 107579

Published: Jan. 5, 2025

The incidence of metabolic diseases-hypertension, diabetes, obesity, dysfunction-associated steatotic liver disease (MASLD), and atherosclerosis-is increasing annually, imposing a significant burden on both human health the social economy. occurrence development these diseases are closely related to disruption ion homeostasis, which is crucial for maintaining cellular functions equilibrium. However, specific mechanism homeostasis in still unclear. This article reviews role pathogenesis assesses its potential as therapeutic target. Furthermore, explores pharmacological strategies that target channels transporters, including existing drugs emerging under development. Lastly, discusses direction future strategies, possibility gene therapy targeting personalized using novel biomarkers. In summary, provides new perspective approach treatment diseases.

Language: Английский

Citations

0
Aprocitentan mitigates doxorubicin-induced cardiotoxicity by inhibiting cuproptosis, oxidative stress, and mitochondrial impairments via the activation of sirtuin 7 DOI

Yufei Chen,

Rui-Qiang Qi,

Zhao Lin

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 148, P. 114141 - 114141

Published: Jan. 28, 2025

Language: Английский

Citations

0
Integrating cuproptosis and immunosenescence: A novel therapeutic strategy in cancer treatment DOI
Ali Ahmadizad Firouzjaei, Seyed Hamid Aghaee‐Bakhtiari

Biochemistry and Biophysics Reports, Journal Year: 2025, Volume and Issue: 42, P. 101983 - 101983

Published: March 29, 2025

Language: Английский

Citations

0
Post-translational acylation of proteins in cardiac hypertrophy DOI
Yingqi Liu, Qin Yang, Guo‐Wei He

et al.

Nature Reviews Cardiology, Journal Year: 2025, Volume and Issue: unknown

Published: April 14, 2025

Language: Английский

Citations

0
Sirtuin3 attenuates pressure overload-induced pathological myocardial remodeling by inhibiting cardiomyocyte cuproptosis DOI Creative Commons
Binghui Kong, Xuehui Zheng, Yang Hu

et al.

Pharmacological Research, Journal Year: 2025, Volume and Issue: unknown, P. 107739 - 107739

Published: April 1, 2025

Pathological myocardial remodelling is the initiation of pressure overload-induced heart failure, and its involvement in associated molecular mechanisms remains to be fully elucidated. The aim this study was investigate whether Sirtuin3 (SIRT3) can affect pathological remodeling by regulating cellular cuproptosis potential mechanisms. In study, we found that overload induced pathologic which cardiomyocytes showed a distinct signature accompanied downregulation SIRT3 expression. vitro experiments demonstrated copper ions reduced expression 40% (p<0.01) via lysosomal degradation. vivo validation 35% tissue. And knockdown increased cardiomyocyte apoptosis. contrast, cardiomyocytes-specific overexpression adeno-associated virus vectors attenuated unaffected circulating levels hepatic renal impairment. Mechanistically, reduction become ion-sensitive state cells affecting binding ion transporter proteins microtubule-associated protein 1a/1b-Light chain 3 (LC3) cardiomyocytes. Disturbance homeostasis leads accumulation development cuproptosis. These findings elucidate novel mechanism affects death suggest great SIRT3-regulated prevention or treatment remodeling.

Language: Английский

Citations

0
The Role of Copper Homeostasis and Cuproptosis in Cerebrovascular Diseases :A novel Therapeutic Target DOI
Xiaoling Fang,

Xinyue Wang,

Manzhao Hao

et al.

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177649 - 177649

Published: May 1, 2025

Language: Английский

Citations

0
Elabela alleviates cuproptosis and vascular calcification in vitaminD3- overloaded mice via regulation of the PPAR-γ /FDX1 signaling DOI Creative Commons

Rui-Qiang Qi,

Yufei Chen,

Jing Cheng

et al.

Molecular Medicine, Journal Year: 2024, Volume and Issue: 30(1)

Published: Nov. 20, 2024

Abstract Background Vascular calcification is a crucial pathophysiological process associated with age-related cardiovascular diseases. Elabela, recently identified peptide, has emerged as significant player in the regulation of function and homeostasis. However, effects underlying mechanisms Elabela on vascular remain largely unexplored. Methods In-vivo calcifications C57BL/6J mice (8-week-old) young or aged (72-week-old) SD rats were injected vitamin D3 (VitD3) saline, respectively. Furthermore, VitD3-overloaded received (1 mg/kg/d), peroxisome proliferators-activated receptor-γ (PPAR-γ) activator Rosiglitazone (5 mg/kg/d) copper-ionophore Elesclomol (20 As for in-vitro studies, primary rat smooth muscle cells (VSMCs) isolated from aortas cultured explore role mechanism calcification. Results There marked increases FDX1 Slc31a1 levels both VSMCs during calcification, coinciding rise copper decrease levels. Alizarin red von-Kossa staining indicated that administration effectively hindered progression cuproptosis arterial rings models. Moreover, significantly suppressed osteogenic differentiation calcium deposition strikingly reversed high phosphate-induced augmentation expression, DLAT aggregation well intracellular ion More importantly, exhibited remarkable abilities to prevent mitochondrial dysfunctions by maintaining membrane potential, inhibiting division, reducing ROS production increasing ATP Interestingly, mitigated cellular senescence pro-inflammatory cytokines including IL-1α, IL-1β, IL-6, IL-18 TNF-α, upregulated protein PPAR-γ mice. Administrating inhibitor GW9662 blocking efflux abolished protective effect enhancing FDX1, Slc31a1, Runx2, BMP2. Conclusion plays protecting against activating /FDX1 signaling. supplementation suppression serve effective therapeutic approaches managing related disorders.

Language: Английский

Citations

0