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1.
Stem Cells ; 41(1): 77-92, 2023 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-36208284

RESUMO

Hypoxia as a microenvironment or niche stimulates proliferation of neural stem cells (NSCs). However, the underlying mechanisms remain elusive. Autophagy is a protective mechanism by which recycled cellular components and energy are rapidly supplied to the cell under stress. Whether autophagy mediates the proliferation of NSCs under hypoxia and how hypoxia induces autophagy remain unclear. Here, we report that hypoxia facilitates embryonic NSC proliferation through HIF-1/mTORC1 signaling pathway-mediated autophagy. Initially, we found that hypoxia greatly induced autophagy in NSCs, while inhibition of autophagy severely impeded the proliferation of NSCs in hypoxia conditions. Next, we demonstrated that the hypoxia core regulator HIF-1 was necessary and sufficient for autophagy induction in NSCs. Considering that mTORC1 is a key switch that suppresses autophagy, we subsequently analyzed the effect of HIF-1 on mTORC1 activity. Our results showed that the mTORC1 activity was negatively regulated by HIF-1. Finally, we provided evidence that HIF-1 regulated mTORC1 activity via its downstream target gene BNIP3. The increased expression of BNIP3 under hypoxia enhanced autophagy activity and proliferation of NSCs, which was mediated by repressing the activity of mTORC1. We further illustrated that BNIP3 can interact with Rheb, a canonical activator of mTORC1. Thus, we suppose that the interaction of BNIP3 with Rheb reduces the regulation of Rheb toward mTORC1 activity, which relieves the suppression of mTORC1 on autophagy, thereby promoting the rapid proliferation of NSCs. Altogether, this study identified a new HIF-1/BNIP3-Rheb/mTORC1 signaling axis, which regulates the NSC proliferation under hypoxia through induction of autophagy.


Assuntos
Proteínas de Membrana , Células-Tronco Neurais , Humanos , Proteínas de Membrana/genética , Hipóxia Celular , Hipóxia/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Autofagia , Células-Tronco Neurais/metabolismo , Proliferação de Células , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo
2.
Bioresour Technol ; 104: 775-82, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22154584

RESUMO

Presently lignin is used as fuel but recent interests in biomaterials encourage the use of this polymer as a renewable feedstock in manufacturing. The present study was undertaken to explore the potential applicability of microwaves to isolate lignin from agricultural residues. A central composite design (CCD) was used to optimize the processing conditions for the microwave (MW)-assisted extraction of lignin from triticale straw. Maximal lignin yield (91%) was found when using 92% EtOH, 0.64 N H(2)SO(4), and 148 °C. The yield and chemical structure of MW-extracted lignin were compared to those of lignin extracted with conventional heating. Under similar conditions, MW irradiation led to higher lignin yields, lignins of lower sugar content, and lignins of smaller molecular weights. Except for these differences the lignins resulting from both types of heating exhibited comparable chemical structures. The present findings should provide a clean source of lignin for potential testing in manufacturing of biomaterials.


Assuntos
Grão Comestível/química , Grão Comestível/efeitos da radiação , Lignina/isolamento & purificação , Lignina/efeitos da radiação , Modelos Químicos , Componentes Aéreos da Planta/química , Componentes Aéreos da Planta/efeitos da radiação , Simulação por Computador , Relação Dose-Resposta à Radiação , Lignina/química , Micro-Ondas , Doses de Radiação
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