Mechanism of PI3K/Akt‑mediated mitochondrial pathway in obesity‑induced apoptosis (Review) DOI Open Access
Jiarui Li,

Manyi Sun,

Ming Tang

et al.

Biomedical Reports, Journal Year: 2024, Volume and Issue: 22(3)

Published: Dec. 27, 2024

Obesity is a pervasive global health challenge that substantially reduces the quality of life millions individuals and impedes social economic advancement. an independent risk factor contributes to range chronic non‑communicable metabolic diseases, significantly affecting energy metabolism, mental health, cancer susceptibility, sleep quality, other physiological processes. The PI3K/AKT signaling pathway, significant glucose, lipid, protein metabolism regulator, integral cellular growth, survival, apoptosis. Apoptosis highly regulated form programmed cell death critical for immune maturation tissue repair. present review examines association between obesity, mitochondrial apoptosis elucidate potential mechanisms by which obesity may activate apoptotic pathways. These findings provide theoretical foundation mitigating obesity‑related complications targeting these

Language: Английский

The Interplay Between Endoplasmic Reticulum Stress and Ferroptosis in Neurological Diseases DOI

Tianyu Zhai,

Bingbing Wang,

Caizhen Shi

et al.

Neurochemical Research, Journal Year: 2025, Volume and Issue: 50(2)

Published: Feb. 10, 2025

Language: Английский

Citations

1
Autophagy in High-Fat Diet and Streptozotocin-Induced Metabolic Cardiomyopathy: Mechanisms and Therapeutic Implications DOI Open Access
Rong Zhou, Zhaoming Zhang, Xinjie Li

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1668 - 1668

Published: Feb. 15, 2025

Metabolic cardiomyopathy, encompassing diabetic and obese is an escalating global health concern, driven by the rising prevalence of metabolic disorders such as insulin resistance, type 1 2 diabetes, obesity. These conditions induce structural functional alterations in heart, including left ventricular dysfunction, fibrosis, ultimately heart failure, particularly presence coronary artery disease or hypertension. Autophagy, a critical cellular process for maintaining cardiac homeostasis, frequently disrupted cardiomyopathy. This review explores role autophagy pathogenesis high-fat diet (HFD) streptozotocin (STZ)-induced focusing on non-selective selective pathways, mitophagy, ER-phagy, ferritinophagy. Key proteins genes PINK1, Parkin, ULK1, AMPK, mTOR, ATG7, ATG5, Beclin-1, miR-34a are central to regulation Dysregulated autophagic flux impairs mitochondrial function, promotes oxidative stress, drives fibrosis heart. Additionally, processes lipophagy, regulated PNPLA8, ferritinophagy, modulated NCOA4, play pivotal roles lipid metabolism iron homeostasis. Emerging therapeutic strategies targeting autophagy, plant extracts (e.g., curcumin, dihydromyricetin), endogenous compounds sirtuin 3, LC3), lipid/glucose-lowering drugs, offer promising avenues mitigating effects Despite recent advances, precise mechanisms underlying this context remain poorly understood. A deeper understanding autophagy's regulatory networks, involving these proteins, may lead novel approaches treating

Language: Английский

Citations

1
Role of Gut Microbial Metabolites in Ischemic and Non-Ischemic Heart Failure DOI Open Access
Mohammad Reza Hatamnejad,

Lejla Medzikovic,

Ateyeh Dehghanitafti

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 2242 - 2242

Published: March 2, 2025

The effect of the gut microbiota extends beyond their habitant place from gastrointestinal tract to distant organs, including cardiovascular system. Research interest in relationship between heart and has recently been emerging. secretes metabolites, Trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), bile (BAs), indole propionic acid (IPA), hydrogen sulfide (H2S), phenylacetylglutamine (PAGln). In this review, we explore accumulating evidence on role these secreted metabolites pathophysiology ischemic non-ischemic failure (HF) by summarizing current knowledge clinical studies experimental models. Elevated TMAO contributes HF through TGF-ß/Smad signaling-mediated myocardial hypertrophy fibrosis, impairments mitochondrial energy production, DNA methylation pattern change, intracellular calcium transport. Also, high-level can promote via inflammation, histone methylation-mediated vascular platelet hyperactivity, thrombosis, as well cholesterol accumulation activation MAPK signaling. Reduced SCFAs upregulate Egr-1 protein, T-cell infiltration, HDAC 5 6 activities, leading HF, while reactive oxygen species production hyperactivation caveolin-ACE axis result HF. An altered BAs level worsens contractility, opens permeability transition pores inducing apoptosis, enhances accumulation, eventually exacerbating IPA, inhibition nicotinamide N-methyl transferase expression increased nicotinamide, NAD+/NADH, SIRT3 levels, ameliorate HF; meanwhile, H2S suppressing Nox4 ROS stimulating PI3K/AKT pathway also protect against Furthermore, PAGln affect sarcomere shortening ability myocyte contraction. This emerging field research new avenues for therapies restoring dietary interventions, prebiotics, probiotics, or fecal transplantation such normalizing circulating levels TMAO, SCFA, BAs, H2S, PAGln.

Language: Английский

Citations

0
Tauroursodeoxycholic Acid Confers Protection Against Oxidative Stress via Autophagy Induction in Retinal Pigment Epithelial Cells DOI Creative Commons
Daniella Zubieta,

Cassandra Warden,

Sujoy Bhattacharya

et al.

Current Issues in Molecular Biology, Journal Year: 2025, Volume and Issue: 47(4), P. 224 - 224

Published: March 26, 2025

Tauroursodeoxycholic acid (TUDCA) has been shown to protect against oxidative damage in retinal pigment epithelial (RPE) cells. However, the mechanisms by which it mediates these protective effects have not thoroughly investigated context of age-related macular degeneration (AMD) disease onset and progression. We measured LC3-II p62 expression via Western blot immunohistochemistry RPE cells treated with H2O2, TUDCA, or a combination both measure autophagy induction. To determine flux, we LC3-II/LC3-I presence bafilomycin blot. mechanistic pathways TUDCA-induced autophagy, protein regulators (Atg5, Beclin-1, S6, AMPK, Akt) show that TUDCA-mediated induction confers protection mTORC1/mTORC2 independent but depends on Atg5. Our work adds overall understanding cell homeostasis highlights role TUDCA maintaining health.

Language: Английский

Citations

0
Akt mitigates ER stress-instigated cardiac dysfunction via regulation of ferroptosis and mitochondrial integrity in a DHODH-dependent manner DOI
Na Zhou, Li Ma, Wanting Shi

et al.

Life Sciences, Journal Year: 2025, Volume and Issue: unknown, P. 123591 - 123591

Published: March 1, 2025

Language: Английский

Citations

0
Mitochondrial quality control and stress signaling pathways in the pathophysiology of cardio-renal diseases DOI Creative Commons
Isabel Amador‐Martínez, Ana Karina Aranda‐Rivera,

Mauricio Raziel Martínez-Castañeda

et al.

Mitochondrion, Journal Year: 2025, Volume and Issue: unknown, P. 102040 - 102040

Published: April 1, 2025

Mitochondria are essential organelles for cellular function and have become a broad field of study. In cardio-renal diseases, it has been established that mitochondrial dysfunction is primary mechanism leading to these pathologies. Under stress, mitochondria can develop stress response mechanisms maintain quality control (MQC) functions. contrast, the perturbation associated with pathogenesis several diseases. Thus, targeting specific pathways within MQC could offer therapeutic avenue protecting integrity. However, related signaling in axis poorly explored. The limitations include lack reproducibility experimental models disease, incomplete knowledge molecules generate bidirectional damage, temporality study models. Therefore, we believe integration all those limitations, along recent advances (i.e., mitophagy), (e.g., integrated response, unfolded protein import), pharmacology, targeted approaches reveal what deregulation like provide ideas generating strategies seek avoid progression

Language: Английский

Citations

0
Natural products and ferroptosis: A novel approach for heart failure management DOI
Zeyu Zhang, Zhihua Yang, Shuai Wang

et al.

Phytomedicine, Journal Year: 2025, Volume and Issue: unknown, P. 156783 - 156783

Published: April 1, 2025

Language: Английский

Citations

0
Impact of the local renin–angiotensin system in perivascular adipose tissue on vascular health and disease DOI
Pitchai Balakumar, Khalid Orayj, Noohu Abdulla Khan

et al.

Cellular Signalling, Journal Year: 2024, Volume and Issue: 124, P. 111461 - 111461

Published: Oct. 9, 2024

Language: Английский

Citations

2
Activation of Protein Kinase B Rescues against Thapsigargin-Elicited Cardiac Dysfunction through Regulation of NADPH Oxidase and Ferroptosis DOI
Xiaohu Wang, Fengjuan Li, Yong Cheng

et al.

Chemico-Biological Interactions, Journal Year: 2024, Volume and Issue: unknown, P. 111292 - 111292

Published: Oct. 1, 2024

Language: Английский

Citations

1
Mechanism of PI3K/Akt‑mediated mitochondrial pathway in obesity‑induced apoptosis (Review) DOI Open Access
Jiarui Li,

Manyi Sun,

Ming Tang

et al.

Biomedical Reports, Journal Year: 2024, Volume and Issue: 22(3)

Published: Dec. 27, 2024

Obesity is a pervasive global health challenge that substantially reduces the quality of life millions individuals and impedes social economic advancement. an independent risk factor contributes to range chronic non‑communicable metabolic diseases, significantly affecting energy metabolism, mental health, cancer susceptibility, sleep quality, other physiological processes. The PI3K/AKT signaling pathway, significant glucose, lipid, protein metabolism regulator, integral cellular growth, survival, apoptosis. Apoptosis highly regulated form programmed cell death critical for immune maturation tissue repair. present review examines association between obesity, mitochondrial apoptosis elucidate potential mechanisms by which obesity may activate apoptotic pathways. These findings provide theoretical foundation mitigating obesity‑related complications targeting these

Language: Английский

Citations

0