Vitamin D attenuates diabetic myocardial injury via the Erbb4/ferroptosis axis DOI Open Access

Hanlu Song,

Yufan Miao,

Yujing Zhang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 12, 2023

Abstract Background Hyperglycemia and hyperlipidemia lead to the ferroptosis, well as phosphorylation of Erbb4, thereby increase risk cardiac hypertrophy. Thus, our investigation aims explore whether vitamin D could mitigate diabetic injury through modulation Erbb4/ferroptosis axis. Methods results KKAy mice fed on a high-fat diet were utilized construct prediabetic model, which showed an up-regulated with concurrent ferroptosis in tissues. Following intervention for 16 weeks, activity Erbb4/YAP signaling was suppressed severeness improved. Meanwhile disturbances glucose-lipid metabolism insulin secretion induced by high fat alleviated, along improvements hypertrophy myocardial function. Moreover, we established vitro damage model introducing H9c2 cells glucose (HG, 33.3 mM) palmitic acid (PA, 0.25 mM). Unsurprisingly, similar have been acquired after supplementation. Subsequently, selective inhibitors Erbb4 (Dacomitinib) (Ferrostatin-1) applied evaluate efficiency modulating , conclusively confirming that inhibiting indeed reduce under HG PA stimulus. Additionally, treatment found cardiomyocyte prevent cell death activity. Interestingly, combined Vitamin Dacomitinib exerted synergistic effect ameliorating abnormal conditions. Conclusions Our study unveils, correlation between heart. Providing evidences supplementation can improve related inactivation Erbb4. Proposing combination may emerge highly feasible clinical strategy injury.

Language: Английский

Vitamin D as a Modulator of Neuroinflammation: Implications for Brain Health DOI
Sebastián García Menéndez, Walter Manucha

Current Pharmaceutical Design, Journal Year: 2024, Volume and Issue: 30(5), P. 323 - 332

Published: Feb. 1, 2024

Abstract: Neuroinflammation represents a critical immune response within the brain, playing pivotal role in defense against injury and infection. However, when this becomes chronic, it can contribute to development of various neurodegenerative psychiatric disorders. This bibliographic review delves into vitamin D modulating neuroinflammation its implications for brain health, particularly context neurological While is traditionally associated with calcium homeostasis bone also exerts immunomodulatory neuroprotective effects central nervous system. Through comprehensive analysis preclinical clinical studies, we uncover how D, acting through receptors glial cells, may influence production proinflammatory cytokines antioxidants, potentially mitigating cascade events leading neuronal damage. Clinical research has identified deficiency as common thread increased risks multiple sclerosis, Parkinson's disease, Alzheimer's, depression, among others. Furthermore, models suggest D's regulatory capacity over inflammatory mediators, protective apoptosis, contribution neurogenesis synaptic plasticity. These insights underscore potential supplementation not only slowing progression diseases but improving quality life patients suffering from conditions. Future studies are essential validate these findings further our understanding prevent or alleviate symptoms, opening new avenues therapeutic strategies neuroinflammation-related pathologies. crucial injuries infections, persistence lead such Parkinson's, depression. Cholecalciferol (Vitamin D3) emerges regulator neuroinflammation, present cells astrocytes microglia, function. Vitamin mechanisms action include cytokine modulation regulation nuclear mitochondrial genes. It adjusts mediators resulting effects. Additionally, impacts neurotransmitter synthesis positions adjunct treating like Alzheimer's Parkinson's. Lastly, intestinal microbiota serotonin contributes disorders schizophrenia Thus, presents novel approach neuroinflammatory, neurodegenerative, neuropsychiatric diseases.

Language: Английский

Citations

13
Targeted ErbB4 receptor activation prevents D-galactose-induced neuronal senescence via inhibiting ferroptosis pathway DOI Creative Commons

Ji-Ji Dao,

Wei Zhang, Chong Liu

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 31, 2025

Neuronal senescence is a common pathological feature of various neurodegenerative diseases, with ferroptosis playing significant role. This study aims to investigate the role ErbB4 receptor activation in preventing D-Galactose (D-gal)-induced neuronal senescence. Mice subjected D-gal-induced aging were administered small molecule agonist (E4A), identified via virtual screening, melatonin, or combination both. Behavioral assessments conducted evaluate therapeutic efficacy memory and cognitive functions. Immunofluorescence staining, western blot, biochemical assays primarily employed assess changes both senescence- ferroptosis-related molecules mouse hippocampal tissues response each treatment. Additionally, HT22 cell cultures utilized corroborate vivo findings. The targeted by E4A significantly ameliorated behavioral deficits induced D-gal mice, demonstrating an effect comparable that natural inhibitor ferroptosis. Both melatonin mitigated neurons mice. was evidenced upregulation Lamin B1 downregulation P53, P21, P16, GFAP, Iba-1 expression levels. Moreover, treatment markedly decreased protein Nrf2 while augmenting promoter TFRC. These alterations partially reversed individual administration melatonin. In vitro studies further corroborated concurrently markers promoters. However, able reverse these changes. Erastin-induced cells. Our findings suggest may be viable strategy for treating inhibiting ferroptosis, thereby offering potential avenue senescence-associated diseases.

Language: Английский

Citations

1
COVID-19 and our understanding of vitamin D and immune function DOI Creative Commons
Martin Hewison

The Journal of Steroid Biochemistry and Molecular Biology, Journal Year: 2025, Volume and Issue: 249, P. 106710 - 106710

Published: Feb. 20, 2025

The interaction between vitamin D and the immune system is perhaps most well recognised extraskeletal facet of D, encompassing early studies therapy for TB leprosy through to more recent links with autoimmune disease. However, spotlight on function has been particularly intense in last five years following COVID-19 pandemic. This was due, part, many association status infection disease prognosis, as smaller number clinical trials supplementation. a potential role also stemmed from basic biology that provides plausible mechanistic rationale beneficial effects improved health setting respiratory infection. aim this review summarise different strands evidence supporting effect COVID-19, how modified during pandemic itself, new aspects are likely arise near future. Key topics feature are: antibacterial versus antiviral innate responses 1,25-dihydroxyvitamin (1,25(OH)2D); 1α-hydroxylase (CYP27B1) activity metabolism 25-hydroxyvitamin (25(OH)D) beyond antigen-presenting cells; advances cell target gene (notably changes metabolic profile). Whilst much interest era focused public health, continued evolution our understanding interacts components continues support health.

Language: Английский

Citations

1
Ferroptosis regulation by Cap’n’collar family transcription factors DOI Creative Commons
Magdalena Murray, Scott J. Dixon

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: 300(8), P. 107583 - 107583

Published: July 16, 2024

Ferroptosis is an iron-dependent cell death mechanism that may be important to prevent tumor formation and useful as a target for new cancer therapies. Transcriptional networks play crucial role in shaping ferroptosis sensitivity by regulating the expression of transporters, metabolic enzymes, other proteins. The Cap'n'collar (CNC) protein nuclear factor erythroid 2 like (NFE2L2, also known NRF2) key regulator many cells contexts. Emerging evidence indicates related CNC family members BTB homology 1 (BACH1) (NFE2L1) have non-redundant roles regulation. Here, we comprehensively review transcription factors governing cellular ferroptosis. We describe how regulate through modulation iron, lipid, redox metabolism. use examples regulation proteins illustrate flexible highly context-dependent nature between conditions.

Language: Английский

Citations

5
Phytic acid-loaded polyvinyl alcohol hydrogels promotes wound healing of injured corneal epithelium through inhibiting ferroptosis DOI Creative Commons

Danni Gong,

Nianxuan Wu,

Huan Chen

et al.

Redox Biology, Journal Year: 2024, Volume and Issue: unknown, P. 103354 - 103354

Published: Sept. 1, 2024

Language: Английский

Citations

5
Ferroptosis in neurodegenerative diseases: mechanisms and therapeutic potential of stem cell derivatives DOI Creative Commons
Ting Zhang, Yun Zhang,

Jinpeng Xie

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: March 21, 2025

Ferroptosis, a non-apoptotic, iron-dependent form of regulated cell death, is closely related to the pathogenesis neurodegenerative diseases. Stem cells and their derivatives exhibit remarkable potential in modulating ferroptosis, offering promising therapeutic intervention for In this review, we systematically explore neurological aging its association with cognitive impairment diseases, focus on molecular mechanisms ferroptosis diseases strategies stem

Language: Английский

Citations

0
Targeting LINC00707 by vitamin D3 attenuates nitrogen mustard-caused dermal toxicity through inhibiting ferroptosis DOI Creative Commons
Xunhu Dong, Ying He,

Xiaofeng Hu

et al.

Redox Biology, Journal Year: 2025, Volume and Issue: unknown, P. 103628 - 103628

Published: April 1, 2025

Nitrogen mustard (NM) causes severe skin injury that is lack of effective and targeted therapies. Vitamin D3 (VD3) emerges as a promising treatment option for NM-caused dermal toxicity; however, the underlying mechanisms are currently unclear. Herein, we identified NM markedly promoted ferroptosis by measurement decreased cell viability, glutathione, glutathione peroxidase 4 solute carrier family 7 member 11 levels, increased ROS, lipid iron/Fe2+ malondialdehyde contents in vitro vivo. Ferrostin-1 (Fer-1, inhibitor) attenuated death keratinocytes. Meanwhile, significantly inhibited phosphorylation AKT1 glycogen synthase kinase 3β (GSK3β) nuclear factor erythroid 2-related 2 (Nrf2) translocation, LINC00707 expression. Furthermore, NM-induced keratinocytes was abolished with agonists Nrf2 (tBHQ) (SC79), inhibitor GSK3β (AR-A014418), overexpression or knockdown. Mechanistically, directly bound protein domain suppressed its activated thereby inactivating Nrf2, subsequently inducing NM-treated Moreover, VD3 notably expression, inactivated GSK3β, translocation cytotoxicity induced The protective effects against toxicity were blocked erastin (a inducer), siRNA, enhanced knockdown Fer-1 In conclusion, ameliorated inhibiting ferroptosis, which partially mediated through LINC00707-AKT1-GSK3β-Nrf2 signaling pathway.

Language: Английский

Citations

0
Vitamin D receptor upregulation promotes ferroptosis-related salivary hyposecretion caused by Sod1 knockout in female mice DOI

Ziyu Han,

Aolin Yang, Jian Yang

et al.

Free Radical Biology and Medicine, Journal Year: 2025, Volume and Issue: 235, P. 124 - 136

Published: April 26, 2025

Language: Английский

Citations

0
Exploring the Association Between Aging, Ferroptosis, and Common Age-Related Diseases DOI

Laleh Mavaddatiyan,

Saghi Hakimi Naeini,

Sara Khodabandeh

et al.

Archives of Gerontology and Geriatrics, Journal Year: 2025, Volume and Issue: 135, P. 105877 - 105877

Published: April 28, 2025

Language: Английский

Citations

0
Vitamin D3 Attenuates Neuropathic Pain via Suppression of Mitochondria‐Associated Ferroptosis by Inhibiting PKCα/NOX4 Signaling Pathway DOI Creative Commons
Wencui Zhang, Shangchen Yu, Bo Jiao

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(9)

Published: Sept. 1, 2024

ABSTRACT Aims Neuropathic pain remains a significant unmet medical challenge due to its elusive mechanisms. Recent clinical observations suggest that vitamin D (VitD) holds promise in relief, yet precise mechanism of action is still unclear. This study explores the therapeutical role and potential VitD 3 spared nerve injury (SNI)‐induced neuropathic rat model. Methods The analgesic effects underlying mechanisms were evaluated SNI naïve models. Mechanical allodynia was assessed using Von Frey test. Western blotting, immunofluorescence, biochemical assay, transmission electron microscope (TEM) employed investigate molecular cellular . Results Ferroptosis observed spinal cord following SNI. Intrathecal administration , active form VitD, activated receptor (VDR), suppressed ferroptosis, alleviated mechanical nociceptive behaviors. treatment preserved GABAergic interneurons, neuroprotective eliminated by ferroptosis inducer RSL3. Additionally, mitigated aberrant mitochondrial morphology oxidative metabolism cord. Mechanistically, inhibited SNI‐induced activation PKCα/NOX4 signaling. Inhibition signaling hypersensitivity, accompanied reduced dysfunction rats. Conversely, rats induced hyperalgesia, loss cord, all which reversed treatment. Conclusions Our findings provide evidence attenuates preserving interneurons through suppression mitochondria‐associated mediated signaling, probably via VDR activation. alone or combination with existing analgesics, presents an innovative therapeutic avenue for pain.

Language: Английский

Citations

3