Twig G, Elorza A, Molina AJ, Mohamed H, Wikstrom JD, Walzer G, Stiles L, Haigh SE, Katz S, Las G, Alroy J, Wu M, Py BF, Yuan J, Deeney JT, Corkey BE, Shirihai OS (2008) Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. Ĭhen H, Detmer SA, Ewald AJ, Griffin EE, Fraser SE, Chan DC (2003) Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development. Palmer CS, Osellame LD, Stojanovski D, Ryan MT (2011) The regulation of mitochondrial morphology: intricate mechanisms and dynamic machinery. Mai S, Klinkenberg M, Auburger G, Bereiter-Hahn J, Jendrach M (2010) Decreased expression of Drp1 and Fis1 mediates mitochondrial elongation in senescent cells and enhances resistance to oxidative stress through PINK1. Navratil M, Terman A, Arriaga EA (2008) Giant mitochondria do not fuse and exchange their contents with normal mitochondria. Unterluggauer H, Hutter E, Voglauer R, Grillari J, Voth M, Bereiter-Hahn J, Jansen-Durr P, Jendrach M (2007) Identification of cultivation-independent markers of human endothelial cell senescence in vitro. Seo AY, Joseph A-M, Dutta D, Hwang JCY, Aris JP, Leeuwenburgh C (2010) New insights into the role of mitochondria in aging: mitochondrial dynamics and more.
FISSION MAC SERIAL FREE
Liochev SI (2013) Reactive oxygen species and the free radical theory of aging. Liu L, Rando TA (2011) Manifestations and mechanisms of stem cell aging. Werner N, Kosiol S, Schiegl T, Ahlers P, Walenta K, Link A, Bohm M, Nickenig G (2005) Circulating endothelial progenitor cells and cardiovascular outcomes. Įrusalimsky JD (2009) Vascular endothelial senescence: from mechanisms to pathophysiology. Īsahara T, Masuda H, Takahashi T, Kalka C, Pastore C, Silver M, Kearne M, Magner M, Isner JM (1999) Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Eur J Nucl Med Mol Imaging 32(Suppl 2):S404–S416. Enhanced expression of Fis1 in senescent EPCs restores the youthful phenotype.īengel FM, Schachinger V, Dimmeler S (2005) Cell-based therapies and imaging in cardiology. In human EPCs, down-regulation of Fis1 is involved in mitochondrial dysfunction and contributes to the impaired activity of EPCs during the senescence process. Fis1 over-expression in senescent EPCs reduced the oxidative stress, increased the proliferation, and restored the cobble stone-like morphology, senescence, bioenergetics, angiogenic potential, and therapeutic activity. Silencing of Fis1 in the young EPCs using Fis1-specific siRNA leads to appearance of phenotype resembling those of senescent cells, including elevated oxidative stress, disturbed mitochondrial network, reduced mitochondria membrane potential, decreasing ATP content, lower proliferation activity, and loss of therapeutic potential in ischemic hindlimbs. In rat EPCs, the Fis1 level was decreased in the animals aged 24 months or older, compared to those of 3 months. Immunoblotting of the senescent EPCs demonstrated decreased expression level of fission protein1 (Fis1). Examination of mitochondrial network showed that senescence increased the length of the network and ultrastructure analysis exhibited elongated mitochondria.
Flow cytometry indicated increased content of reactive oxygen species, mitochondria, and calcium, while bioenergetic analysis showed increased oxygen consumption and reduced ATP content. The senescent cells, in medium free of glucose and bicarbonate, showed impaired activity in migration and tube formation.
FISSION MAC SERIAL SERIAL
Serial passage increased cell doubling time and those cells reaching the doubling time for more than 100% were defined as senescent EPCs, of which the activity of therapeutic angiogenesis was attenuated in mouse ischemic hindlimbs. We investigated the contribution of mitochondrial dysfunction to the senescence of human endothelial progenitor cells (EPCs) expanded in vitro and the underlying molecular mechanism.
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