http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
The Nrf2 antioxidant defense system in intervertebral disc degeneration: Molecular insights
Xiang Qian,Zhao Yongzhao,Lin Jialiang,Jiang Shuai,Li Weishi 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-
Intervertebral disc degeneration (IDD) is a common degenerative musculoskeletal disorder and is recognized as a major contributor to discogenic lower back pain. However, the molecular mechanisms underlying IDD remain unclear, and therapeutic strategies for IDD are currently limited. Oxidative stress plays pivotal roles in the pathogenesis and progression of many age-related diseases in humans, including IDD. Nuclear factor E2-related factor 2 (Nrf2) is a master antioxidant transcription factor that protects cells against oxidative stress damage. Nrf2 is negatively modulated by Kelch-like ECH-associated protein 1 (Keap1) and exerts important effects on IDD progression. Accumulating evidence has revealed that Nrf2 can facilitate the transcription of downstream antioxidant genes in disc cells by binding to antioxidant response elements (AREs) in promoter regions, including heme oxygenase-1 (HO-1), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and NADPH quinone dehydrogenase 1 (NQO1). The Nrf2 antioxidant defense system regulates cell apoptosis, senescence, extracellular matrix (ECM) metabolism, the inflammatory response of the nucleus pulposus (NP), and calcification of the cartilaginous endplates (EP) in IDD. In this review, we aim to discuss the current knowledge on the roles of Nrf2 in IDD systematically.
Lin Jialiang,Wang Longjie,Wu Yuhao,Xiang Qian,Zhao Yongzhao,Zheng Xuanqi,Jiang Shuai,Sun Zhuoran,Fan Dongwei,Li Weishi 생화학분자생물학회 2024 Experimental and molecular medicine Vol.56 No.-
Intervertebral disc degeneration (IDD) is an important pathological basis for degenerative spinal diseases and is involved in mitophagy dysfunction. However, the molecular mechanisms underlying mitophagy regulation in IDD remain unclear. This study aimed to clarify the role of DJ-1 in regulating mitophagy during IDD pathogenesis. Here, we showed that the mitochondrial localization of DJ-1 in nucleus pulposus cells (NPCs) first increased and then decreased in response to oxidative stress. Subsequently, loss- and gain-of-function experiments revealed that overexpression of DJ-1 in NPCs inhibited oxidative stress-induced mitochondrial dysfunction and mitochondria-dependent apoptosis, whereas knockdown of DJ-1 had the opposite effect. Mechanistically, mitochondrial translocation of DJ-1 promoted the recruitment of hexokinase 2 (HK2) to damaged mitochondria by activating Akt and subsequently Parkin-dependent mitophagy to inhibit oxidative stress-induced apoptosis in NPCs. However, silencing Parkin, reducing mitochondrial recruitment of HK2, or inhibiting Akt activation suppressed DJ-1-mediated mitophagy. Furthermore, overexpression of DJ-1 ameliorated IDD in rats through HK2-mediated mitophagy. Taken together, these findings indicate that DJ-1 promotes HK2-mediated mitophagy under oxidative stress conditions to inhibit mitochondria-dependent apoptosis in NPCs and could be a therapeutic target for IDD.
Production and Characterization of Extracellular Chitin Deacetylase from Absidia corymbifera DY-9
( Yong Zhao ),( Young Ju Kim ),( Kyung Taek Oh ),( Van Nam Nguyen ),( Ro Dong Park ) 한국응용생명화학회 2010 Applied Biological Chemistry (Appl Biol Chem) Vol.53 No.2
Recent attention has been paid to the screening of chitin deacetylase (CDA) from fungi, which may be applied into industrial production of chitosan and chitosan oligomers. We screened an extracellular CDA from a fungus that was further identified to be Absidia corymbifera DY-9. CDA from A. corymbifera DY-9 exhibited a higher enzyme activity than that of Mucor rouxii CDA. The highest yield of CDA was achieved in a liquid medium containing 2% powder chitin at pH 9.0, 28˚C and 150 rpm. Moreover, the biochemical properties of this enzyme were studied. It was found that the optimal pH and temperature were 6.5 and 55˚C. The enzyme activity could be enhanced in the presence of 1-10 mM Co2+, Ca2+ and Mg2+ while inhibited by acetate and EDTA. The enzyme was active on WSCT-50, glycol chitin, chitosan (DDA 71-88 %) and chitin oligosaccharides with a DP no less than 2.