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Osteoclast precursor differentiation by MCPIP via oxidative stress,endoplasmic reticulum stress,and autophagy

Journal of Molecular Cell Biology 2011年第6期3卷 360-368页

作者： Kangkai Wang Jianli Niu hyunbae kim Pappachan E.Kolattukudy Burnett School of Biomedical Sciences College of MedicineUniversity of Central FloridaOrlandoFL 32816USA

Osteoclasts(OCs)are responsible for bone resorption in inflammatory joint *** chemotactic protein-1(MCP-1)has been shown to induce differentiation of monocytes to OC precursors,but nothing is known about the underlying ***,we elucidate how MCPIP,induced by MCP-1,mediates this *** of MCPIP abolished MCP-1-mediated expression of OC markers,tartrate-resistant acid phosphatase,and serine protease cathepsin *** of MCPIP induced p47PHOX and its membrane translocation,reactive oxygen species formation,and induction of endoplasmic reticulum(ER)stress chaperones,up-regulation of autophagy marker,Beclin-1,and lipidation of LC3,and induction of OC *** of oxidative stress attenuated ER stress and autophagy,and suppressed expression of OC *** of ER stress by a specific inhibitor or by knockdown of IRE1 blocked autophagy and induction of OC *** stress inducers,tunicamycin and thapsigargin,induced expression of OC *** inhibition by 3′-methyladenine,LY294002,wortmannin or by knockdown of Beclin-1 or Atg 7 inhibited MCPIP-induced expression of OC *** results strongly suggest that MCP-1-induced differentiation of OC precursor cells is mediated via MCPIP-induced oxidative stress that causes ER stress leading to autophagy,revealing a novel mechanistic insight into the role of MCP-1 in OCs differentiation.

关键词： MCP-1 MCPIP osteoclast differentiation reactive oxygen species ER stress

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Interaction between stress responses and circadian metabolism in metabolic disease

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Liver Research 2017年第3期1卷 156-162页

作者： Zhao Yang hyunbae kim Arushana Ali Ze Zheng Kezhong Zhang Center for Molecular Medicine and Genetics Wayne State University School of MedicineMIUSA Department of Microbiology Immunologyand BiochemistryWayne State University School of MedicineMIUSA Karmanos Cancer Institute Wayne State University School of MedicineDetroitMIUSA

Circadian rhythms play crucial roles in orchestrating diverse physiological processes that are critical for health and *** circadian rhythms are closely associated with various human metabolic diseases,including type 2 diabetes,cardiovascular disease,and non-alcoholic fatty liver *** lifestyles are frequently associated with an irregular circadian rhythm,which poses a significant risk to public *** the central clock has a set periodicity,circadian oscillators in peripheral organs,particularly in the liver,can be entrained by metabolic alterations or stress *** the molecular level,the signal transduction pathways that mediate stress responses interact with the key determinants of circadian oscillation to maintain metabolic homeostasis under physiological or pathological *** the liver,a number of nuclear receptors or transcriptional regulators,which are regulated by metabolites,hormones,the circadian clock,or environmental stressors,serve as direct links between stress responses and circadian *** this review,we summarize recent advances in the understanding of the interactions between stress responses(endoplasmic reticulum stress response,oxidative stress response,and inflammatory responses)and circadian metabolism,and the role of these interactions in the development of metabolic diseases.

关键词： Stress response Circadian metabolism Metabolic disease Non-alcoholic fatty liver disease(NAFLD) Hepatic lipid metabolism

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