Abstract Mitochondrial dysfunction contributes to the development of secondary brain injury (SBI) following intracerebral hemorrhage (ICH) and represents a promising therapeutic target. Celastrol, primary active component Tripterygium wilfordii , is natural product that exhibits mitochondrial neuronal protection in various cell types. This study aims investigate neuroprotective effects celastrol against ICH‐induced SBI explore its underlying mechanisms. Celastrol improves neurobehavioral...

Angelman syndrome (AS) is a neurodevelopment disorder characterized by severe cognitive impairment and high rate of autism. AS caused disrupted neuronal expression the maternally inherited Ube3A ubiquitin protein ligase, required for proteasomal degradation proteins implicated in synaptic plasticity, such as activity-regulated cytoskeletal-associated (Arc/Arg3.1). Mice deficient maternal express elevated levels Arc response to activity, which coincides with severely impaired long-term...

Abstract SIRT1 is a member of highly conserved gene family (sirtuins) encoding nicotinamide adenine dinucleotide (NAD) + ‐dependent deacetylases, originally found to deacetylate histones leading increased DNA stability and prolonged survival in yeast higher organisms, including mammals. has been function as deacetylase for numerous protein targets involved various cellular pathways, stress responses, apoptosis axonal degeneration. However, the role ultraviolet (UV) signalling pathways...

VEGF binding to VEGFR2 leads endocytosis and downstream signaling activation promote angiogenesis. Methods: Using genetic strategies, we tested the requirement of α subunits heterotrimeric G proteins (Gαi1/3) in process. Results: Gαi1/3 are located complex (VEGFR2-Ephrin-B2-Dab2-PAR-3), where they required for transduction. knockdown, knockout or dominant negative mutation inhibited VEGF-induced endocytosis, Akt-mTOR Erk-MAPK activation. Functional studies show that shRNA proliferation,...

HBO1 (KAT7 or MYST2) is a histone acetyltransferase that acetylates H3 and H4 histones. Methods: expression was tested in human OS tissues cells. Genetic strategies, including shRNA, CRISPR/Cas9 overexpression constructs, were applied to exogenously alter The inhibitor WM-3835 utilized block activation. Results:HBO1 mRNA protein significantly elevated In established (MG63/U2OS lines) primary cells, shRNA-mediated silencing CRISPR/Cas9-induced knockout able potently inhibit cell viability,...

Signaling mediated by brain-derived neurotrophic factor (BDNF), which is supported the postsynaptic scaffolding protein PSD-95, has antidepressant effects. Conversely, clinical depression associated with reduced BDNF signaling. We found that peptidomimetic compounds bind to PSD-95 promoted signaling receptor TrkB in hippocampus and depression-like behaviors mice. The CN2097 Syn3 both PDZ3 domain of also binds an α-helical region protein. two mouse models stress-induced depression; had...

Abstract Inflammatory responses and neuronal ferroptosis, which are associated with abnormal accumulation of reactive oxygen species (ROS), exert crucial damaging effects on the brain after intracerebral hemorrhage (ICH). In this study, minocycline (MC)‐loaded cerium oxide nanoparticles (CeO 2 ‐MC) constructed for combined ICH treatment. Ultra‐small CeO (≈5 nm) synthesized via a high‐temperature approach exhibits powerful free‐radical scavenging iron‐chelating abilities. vitro experiments...

Two members of the Gα i family G proteins form complexes with EGFR and adaptor protein Gab1 to mediate activation Akt.

AQP3 (aquaporin-3), known as an integral membrane channel in epidermal keratinocytes, facilitates water and glycerol movement into out of the skin. Here, we demonstrate that is also expressed cultured human skin fibroblasts, which under normal wound healing processes migrate from surrounding tissues to close wound. EGF (epidermal growth factor), induced fibroblast migration, expression a time- dose-dependent manner. CuSO4 NiCl2, previously transport inhibitors, well two other bivalent heavy...

AMP-activated protein kinase or AMPK is an evolutionarily conserved sensor of cellular energy status, activated by a variety stresses that deplete ATP. However, the possible involvement in UV- and H(2)O(2)-induced oxidative lead to skin aging cancer has not been fully studied. We demonstrated for first time UV H(2)O(2) induce activation (Thr(172) phosphorylation) cultured human keratinocytes. also phosphorylate LKB1, upstream signal AMPK, epidermal growth factor receptor-dependent manner....

Abstract One of the major characteristics human skin photoaging induced by ultraviolet (UV) radiation is dehydration skin. Water movement across plasma membrane occurs via diffusion through lipid bilayer and aquaporins (AQPs). We find that UV induces aquaporin‐3 (AQP3) down‐regulation in keratinocytes. MEK/ERK inhibitors PD98059 U0126 inhibit UV‐induced AQP3. Antioxidant N ‐acetyl‐ L ‐cysteine or NAC blocks activation All‐trans retinoic acid atRA, while alone inducing AQP3 expression,...

A major challenge to nanomaterial-based medicine is the ability release drugs on-command. Here, we describe an innovative drug delivery system based on carbon nanotubes (CNTs), in which compounds can be released inside cells from within nanotube "on-command" by inductive heating with external alternating current or pulsed magnetic field. Without remains safely CNTs, showing no toxicity cell viability tests. Similar "Trojan-Horse" function, demonstrate of a combination chemotherapeutic agents...

Excessive UV radiation and reactive oxygen species (ROS) cause retinal pigment epithelium (RPE) cell injuries. Nrf2 regulates transcriptional activation of many anti-oxidant genes. Here, we tested the potential role 3H-1,2-dithiole-3-thione (D3T) against or ROS damages in cultured RPE cells (both primary ARPE-19 line). We showed that D3T significantly inhibited UV-/H2O2-induced death apoptosis. UV-stimulated production was dramatically by pretreatment. induced phosphorylation cells, causing...

// Yi-qing Gong 1, 2, * , Wei Huang Ke-ran Li Yuan-yuan Liu 3, Guo-fan Cao 1 Cong 3 Qin Jiang The Affiliated Eye Hospital of Nanjing Medical University, Nanjing, China 2 Ophthalmology Department, Zhenjiang First People's Hospital, Zhenjiang, Institute Neuroscience, Soochow Suzhou, Jiangsu, These authors contributed equally to this work Correspondence to: Jiang, email: Jqin710@vip.sina.com Cao, 1548397844@qq.com caocong@suda.edu.cn Keywords: retinal pigment epithelium, UV, SC79, Akt, Nrf2...

Abnormal activation of neddylation modification and dysregulated energy metabolism are frequently seen in many types cancer cells. Whether how affects cellular remains largely unknown. Here, we showed that MLN4924, a small-molecule inhibitor modification, induces mitochondrial fission-to-fusion conversion breast cells via inhibiting ubiquitylation degradation fusion-promoting protein mitofusin 1 (MFN1) by SCFβ-TrCP E3 ligase blocking the translocation fusion-inhibiting DRP1. Importantly,...

Significance Heterotrimeric Gαi proteins are known to transduce G protein-coupled receptor signals. We have identified a role for in mediating brain-derived neurotrophic factor (BDNF)–tropomyosin-related kinase B (TrkB) signaling. BDNF dysfunction contributes the pathophysiology of depression. In stress model depression Gαi1 and Gαi3 downregulated hippocampus, limbic structure associated with major depressive disorder. show that Gαi1/Gαi3 required TrkB downstream signaling, knockout mice...

Neuroligin-3 (NLGN3) is necessary and sufficient to promote glioma cell growth.The recruitment of Gαi1/3 the ligand-activated receptor tyrosine kinases (RTKs) essential for mediating oncogenic signaling.Methods: Various genetic strategies were utilized examine requirement in NLGN3-driven growth.Results: NLGN3-induced Akt-mTORC1 Erk activation was inhibited by decreasing expression.In contrast ectopic overexpression enhanced signaling.In cells, growth, proliferation migration attenuated...

IL-4 induces Akt activation in macrophages, required for full M2 (alternative) polarization. We examined the roles of Gαi1 and Gαi3 polarization using multiple genetic methods. Methods Results: In MEFs primary murine BMDMs, Gαi1/3 shRNA, knockout or dominant negative mutations attenuated IL-4-induced IL4Rα endocytosis, Gab1 recruitment as well activation, leaving STAT6 signaling unaffected. Following stimulation, proteins associated with intracellular domain IL-4Rα APPL1 adaptor, to mediate...

We here examined the potential biological function of phosphoenolpyruvate carboxykinase 1 (PCK1) in angiogenesis. shRNA- or CRISPR-Cas9–induced PCK1 depletion potently inhibited endothelial cell proliferation, migration, sprouting, and tube formation, whereas ectopic overexpression exerted opposite activity. In HUVECs, Gα i3 expression Akt activation were decreased following depletion, but augmented by overexpression. vivo, retinal gradually increased from postnatal day (P1) to P5. The...