Loss of hepatic manganese transporter ZIP8 disrupts serum transferrin glycosylation and the glutamate-glutamine cycle

Powers, Michael R.; Minchella, Dean; Gonzalez-Acevedo, Minelly; Escutia-Plaza, Daisy; Wu, Jiaqi; Heger, Chris; Milne, Ginger L.; Aschner, Michael; Liu, Zijuan

doi:10.1016/j.jtemb.2023.127184

Cited by 2 publications

(1 citation statement)

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“…DMT1 and ZIP8/14 transport Fe 2+ into the cytoplasm. 48 , 49 Aberrant expression of TFR1 and DMT1 serves as a marker of ferroptosis. Here, we investigated the effect of NDSP on iron metabolic pathways and found that NDSP attenuated the imbalance in iron metabolism by decreasing TFR1 and DMT1 expression.…”

Section: Discussionmentioning

confidence: 99%

Naodesheng Pills Ameliorate Cerebral Ischemia Reperfusion-Induced Ferroptosis via Inhibition of the ERK1/2 Signaling Pathway

Yang,

Deng,

Xiang

2024

DDDT

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Background Ferroptosis plays a crucial role in the occurrence and development of cerebral ischemia-reperfusion (I/R) injury and is regulated by mitogen-activated protein kinase 1/2 (ERK1/2). In China, Naodesheng Pills (NDSP) are prescribed to prevent and treat cerebrosclerosis and stroke. However, the protective effects and mechanism of action of NDSP against cerebral I/R-induced ferroptosis remain unclear. We investigated whether NDSP exerts its protective effects against I/R injury by regulating ferroptosis and aimed to elucidate the underlying mechanisms. Methods The efficacy of NDSP was evaluated using a Sprague-Dawley rat model of middle cerebral artery occlusion and an in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) model. Brain injury was assessed using 2,3,5-triphenyltetrazolium chloride (TTC), hematoxylin and eosin staining, Nissl staining, and neurological scoring. Western blotting was performed to determine the expression levels of glutathione peroxidase 4 (GPX4), divalent metal-ion transporter-1 (DMT1), solute carrier family 7 member 11 (SLC7A11), and transferrin receptor 1 (TFR1). Iron levels, oxidative stress, and mitochondrial morphology were also evaluated. Network pharmacology was used to assess the associated mechanisms. Results NDSP (1.08 g/kg) significantly improved cerebral infarct area, cerebral water content, neurological scores, and cerebral tissue damage. Furthermore, NDSP inhibited I/R- and OGD/R-induced ferroptosis, as evidenced by the increased protein expression of GPX4 and SLC7A11, suppression of TFR1 and DMT1, and an overall reduction in oxidative stress and Fe 2+ levels. The protective effects of NDSP in vitro were abolished by the GPX4 inhibitor RSL3. Network pharmacology analysis revealed that ERK1/2 was the core target gene and that NDSP reduced the amount of phosphorylated ERK1/2. Conclusion NDSP exerts its protective effects against I/R by inhibiting cerebral I/R-induced ferroptosis, and this mechanism is associated with the regulation of ferroptosis via the ERK1/2 signaling pathway.

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Section: Discussionmentioning

confidence: 99%