PINK1/Parkin-Mediated Mitophagy Ameliorates Mitochondrial Dysfunction in Lacrimal Gland Acinar Cells During Aging

Investigative Ophthalmology & Visual Science, Journal Year: 2024, Volume and Issue: 65(13), P. 12 - 12

Published: Nov. 6, 2024

Purpose: Aging alters the function of lacrimal gland and disrupts balance microenvironment on ocular surface, eventually leading to aqueous-tear-deficient dry eye. Mitophagy has been reported play an important role in aging, but underlying mechanism remains unclear. Methods: The young (6 weeks) middle-aged (12 months) male C57BL/6J mice were used this study, mitophagy agonist rapamycin inhibitor Mdivi-1 vivo experiments. Hematoxylin eosin, Masson, Oil Red O, reactive oxygen species (ROS) staining detect histological changes lipids gland. Changes expression proteins identified by Western blotting lysates. Transmission electron microscopy immunofluorescence assess mitophagy. single-cell RNA sequencing (scRNA-seq) bioinformatics analyses transcription signature during aging. Results: In we discovered that aging increased oxidative stress, which apoptosis, generated ROS acinar epithelial cells. Furthermore, activation PINK1/Parkin-mediated reduced concentrations prevented aging-induced apoptosis cells, thereby causing alterations, microstructural degradation, increasing tear secretion associated with accumulation. By contrast, aggregates mitochondrial thereafter leads impairment inhibiting fission giving rise Conclusions: Overall, our findings suggested could impair age-related alterations may be treated therapeutic approaches enhance while maintaining function.

Language: Английский

Allium Macrostemon Bge. Attenuates the Cognitive Decline of Aging Mice by Enhancing BDNF/TrkB Pathway

Food Science & Nutrition, Journal Year: 2025, Volume and Issue: 13(3)

Published: Feb. 28, 2025

ABSTRACT Allium macrostemon Bge. (AM) is a widely utilized culinary spice recognized for its numerous health‐promoting properties. Aging‐related cognitive impairment (ARCI) represents significant global health concern during the aging process. However, potential of AM to attenuate ARCI has not been investigated. This work aims reveal effects and mechanisms water extraction (WEAM) in alleviating ARCI, with particular emphasis on BDNF/TrkB signaling pathway. The findings showed enhancement memory function reduction hippocampal neuronal damage mice following treatment WEAM, manifested by an increased spontaneous alternation rate Y‐maze, prolonged step‐through latency, decreased number errors PAT test, shortened escape latency platform swimming time crossing times MWM test. Additionally, WEAM reduced oxidative stress, elevated expression proteins related synaptic plasticity (SYN PSD95), activated pathway D‐galactose‐induced mice. To elucidate mechanism which alleviates both TrkB activator (7,8‐DHF) inhibitor (ANA‐12) were employed. results demonstrated that potentiated 7,8‐DHF diminished ANA‐12. Finally, 11 chemical compositions analyzed quantified using HPLC‐MS/MS, including macrostemonoside, sarsasapogenin, diosgenin, timosaponin AIII, N‐p‐trans‐coumaroyltyramine, guanosine, adenosine, phenylalanine, adenine, arginine, valine. These suggest may serve as promising mitigating promoting pathway, thereby enhancing plasticity.

Language: Английский

Inhibiting H2AX Can Ameliorate Myocardial Ischemia/Reperfusion Injury by Regulating P53/JNK Signaling Pathway

Cardiology Research and Practice, Journal Year: 2024, Volume and Issue: 2024(1)

Published: Jan. 1, 2024

Myocardial ischemia‐reperfusion (I/R) injury is a significant area of focus in cardiovascular disease research. I/R can increase intracellular oxidative stress, leading to DNA damage. H2AX plays crucial role repair. This study utilized mouse and cell models myocardial investigate the impact on cardiomyocytes during I/R. initially assessed expression MI/R mice compared sham surgery group. Subsequently, cardiac function, infarct area, mitochondrial damage were evaluated after inhibiting negative control Furthermore, delved into molecular mechanisms by analyzing H2AX, P53, p‐JNK, SHP2, p‐SHP2, p‐RAS, parkin, Drp1, Cyt‐C, Caspase‐3, Caspase‐8 following addition JNK or P53 agonists. The results from western blotting vivo indicated significantly higher group Inhibiting improved reduced mitigated In vitro experiments demonstrated that could attenuate apoptosis cells modulating signaling pathways. These findings suggested may alleviate through regulation P53/JNK pathway, highlighting as potential target for treatment ischemia/reperfusion injury.

Language: Английский