PHLDA1 knockdown alleviates mitochondrial dysfunction and endoplasmic reticulum stress-induced neuronal apoptosis via activating PPARγ in cerebral ischemia-reperfusion injury

Liu, Yushuang; Zhao, Hanshu; Chen, Nan; Li, Yuelong; Zheng, Zeyang; Sun, Zhigang; Zhang, Zhongling

doi:10.1016/j.brainresbull.2023.01.007

Cited by 6 publications

(2 citation statements)

References 51 publications

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“…Overexpression of Egr1 has been demonstrated to exacerbate ICH-induced cerebral injury [11], however, the mechanism of that remains unclear. Furthermore, Phlda1 is implicated in inhibiting neuronal apoptosis and pyroptosis, processes that can be harmful during brain injuries [16,18]. In order to unravel the internal mechanism of Egr1 and Phlda1 in ICH, we first built an ICH cell model and preliminarily investigated the expression status of Egr1 and Phlda1 within ICH.…”

Section: Resultsmentioning

confidence: 99%

“…Pleckstrin homology-like domain family A member 1 (Phlda1) contains proline-glutamine and proline-histidine repeat domains [13], and has been linked to brain injury [14]. The inhibition of Phlda1 was found to improve ischemia/reperfusion-induced cerebral injury [15,16], and subarachnoid hemorrhage-induced brain injury [17]. Nonetheless, the function of Phlda1 in brain damage caused by ICH remains undefined.…”

Section: Introductionmentioning

confidence: 99%

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Egr1 promotes Nlrc4-dependent neuronal pyroptosis through phlda1 in an in-vitro model of intracerebral hemorrhage

Wang,

Gu,

Jin

et al. 2024

NeuroReport

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Intracerebral hemorrhage (ICH) is a fatal brain injury, but the current treatments for it are inadequate to reduce the severity of secondary brain injury. Our study aims to explore the molecular mechanism of Egr1 and Phlda1 in regulating hemin-induced neuronal pyroptosis, and hope to provide novel therapeutic targets for ICH treatment. Mouse hippocampal neuron cells treated with hemin were used to simulate an in-vitro ICH model. Using qRT-PCR and western blot to evaluate mRNA and protein concentrations. MTT assay was utilized to assess cell viability. LDH levels were determined by lactate Dehydrogenase Activity Assay Kit. IL-1β and IL-18 levels were examined by ELISA. The interaction of Egr1 and Phlda1 promoter was evaluated using chromatin immunoprecipitation and dual-luciferase reporter assays. Egr1 and Phlda1 were both upregulated in HT22 cells following hemin treatment. Hemin treatment caused a significant reduction in HT22 cell viability, an increase in Nlrc4 and HT22 cell pyroptosis, and heightened inflammation. However, knocking down Egr1 neutralized hemin-induced effects on HT22 cells. Egr1 bound to the promoter of Phlda1 and transcriptionally activated Phlda1. Silencing Phlda1 significantly reduced Nlrc4-dependent neuronal pyroptosis. Conversely, overexpressing Phlda1 mitigated the inhibitory effects of Egr1 knockdown on Nlrc4 and neuronal pyroptosis during ICH. Egr1 enhanced neuronal pyroptosis mediated by Nlrc4 under ICH via transcriptionally activating Phlda1.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Egr1 promotes Nlrc4-dependent neuronal pyroptosis through phlda1 in an in-vitro model of intracerebral hemorrhage

Wang,

Gu,

Jin

et al. 2024

NeuroReport

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Expanding on roles of pleckstrin homology-like domain family A member 1 protein

Durbas

2024

Cell Tissue Res

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Pleckstrin homology-like domain, family A, member 1 (PHLDA1), one of the three members of PHLDA (1–3) family, has been reported to be expressed in mammalian cells and tissues and play diverse roles in various biological processes such as apoptosis, pyroptosis, and differentiation. Nevertheless, new roles and mechanisms of PHLDA1 action have come to light, with some needing further clarification. The major aim of the publication is to review proapoptotic or antiapoptotic roles of PHLDA1 in cancer, including ample evidence on PHLDA1 role as a tumor suppressor gene or oncogene and its influence on tumor progression. The role of PHLDA1 as a prognostic marker of cancer emerges, as well as its role in drug response and resistance. PHLDA1 involvement in autophagy, endoplasmic reticulum stress, pyroptosis, or differentiation is also scrutinized. It is also important to note that the association of PHLDA1 with miRNA regulation is described. Additionally, the emerging functions of PHLDA1 are indicated, specifically in inflammation and ischemia/reperfusion injury.

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Unveiling the hidden dangers: a review of non-apoptotic programmed cell death in anesthetic-induced developmental neurotoxicity

Sun,

Yisi Shan,

Cao

et al. 2024

Cell Biol Toxicol

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Anesthetic-induced developmental neurotoxicity (AIDN) can arise due to various factors, among which aberrant nerve cell death is a prominent risk factor. Animal studies have reported that repeated or prolonged anesthetic exposure can cause significant neuroapoptosis in the developing brain. Lately, non-apoptotic programmed cell deaths (PCDs), characterized by inflammation and oxidative stress, have gained increasing attention. Substantial evidence suggests that non-apoptotic PCDs are essential for neuronal cell death in AIDN compared to apoptosis. This article examines relevant publications in the PubMed database until April 2024. Only original articles in English that investigated the potential manifestations of non-apoptotic PCD in AIDN were analysed. Specifically, it investigates necroptosis, pyroptosis, ferroptosis, and parthanatos, elucidating the signaling mechanisms associated with each form. Furthermore, this study explores the potential relevance of these non-apoptotic PCDs pathways to the pathological mechanisms underlying AIDN, drawing upon their distinctive characteristics. Despite the considerable challenges involved in translating fundamental scientific knowledge into clinical therapeutic interventions, this comprehensive review offers a theoretical foundation for developing innovative preventive and treatment strategies targeting non-apoptotic PCDs in the context of AIDN.

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PHLDA1 knockdown alleviates mitochondrial dysfunction and endoplasmic reticulum stress-induced neuronal apoptosis via activating PPARγ in cerebral ischemia-reperfusion injury

Cited by 6 publications

References 51 publications

Egr1 promotes Nlrc4-dependent neuronal pyroptosis through phlda1 in an in-vitro model of intracerebral hemorrhage

Egr1 promotes Nlrc4-dependent neuronal pyroptosis through phlda1 in an in-vitro model of intracerebral hemorrhage

Expanding on roles of pleckstrin homology-like domain family A member 1 protein

Unveiling the hidden dangers: a review of non-apoptotic programmed cell death in anesthetic-induced developmental neurotoxicity

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