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Your search keyword '"Yuan, Youzhong"' showing total 2 results
Start Over Author "Yuan, Youzhong" Topic apoptosis
2 results on '"Yuan, Youzhong"'

1. Deletion of Puma protects hematopoietic stem cells and confers long-term survival in response to high-dose gamma-irradiation.

Author

Yu H, Shen H, Yuan Y, XuFeng R, Hu X, Garrison SP, Zhang L, Yu J, Zambetti GP, and Cheng T

Subjects
Animals, Cell Survival genetics, Cell Survival radiation effects, Gene Deletion, Mice, Mice, Transgenic, Apoptosis genetics, Apoptosis radiation effects, Apoptosis Regulatory Proteins, DNA Repair genetics, DNA Repair radiation effects, Gamma Rays adverse effects, Hematopoietic Stem Cells metabolism, Tumor Suppressor Proteins
Abstract

Molecular paradigms underlying the death of hematopoietic stem cells (HSCs) induced by ionizing radiation are poorly defined. We have examined the role of Puma (p53 up-regulated mediator of apoptosis) in apoptosis of HSCs after radiation injury. In the absence of Puma, HSCs were highly resistant to gamma-radiation in a cell autonomous manner. As a result, Puma-null mice or the wild-type mice reconstituted with Puma-null bone marrow cells were strikingly able to survive for a long term after high-dose gamma-radiation that normally would pose 100% lethality on wild-type animals. Interestingly, there was no increase of malignancy in the exposed animals. Such profound beneficial effects of Puma deficiency were likely associated with better maintained quiescence and more efficient DNA repair in the stem cells. This study demonstrates that Puma is a unique mediator in radiation-induced death of HSCs. Puma may be a potential target for developing an effective treatment aimed to protect HSCs from lethal radiation.

Published
2010
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2. Changes in FADD levels, distribution, and phosphorylation in TNFalpha-induced apoptosis in hepatocytes is caspase-3, caspase-8 and BID dependent.

Author

Zhang X, Vallabhaneni R, Loughran PA, Shapiro R, Yin XM, Yuan Y, and Billiar TR

Subjects
Active Transport, Cell Nucleus drug effects, Active Transport, Cell Nucleus physiology, Animals, Apoptosis drug effects, BH3 Interacting Domain Death Agonist Protein drug effects, Caspase 3 drug effects, Caspase 3 metabolism, Caspase 8 drug effects, Caspase 8 metabolism, Caspases drug effects, Cytoplasm drug effects, Cytoplasm metabolism, Dactinomycin pharmacology, Death Domain Receptor Signaling Adaptor Proteins drug effects, Death Domain Receptor Signaling Adaptor Proteins metabolism, Fas-Associated Death Domain Protein drug effects, Hepatocytes drug effects, Humans, Male, Membrane Potential, Mitochondrial drug effects, Membrane Potential, Mitochondrial physiology, Mice, Mice, Inbred C57BL, Mice, Knockout, Phosphorylation drug effects, Signal Transduction drug effects, Signal Transduction physiology, Tumor Necrosis Factor-alpha drug effects, Up-Regulation drug effects, Up-Regulation physiology, Apoptosis physiology, BH3 Interacting Domain Death Agonist Protein metabolism, Caspases metabolism, Fas-Associated Death Domain Protein metabolism, Hepatocytes metabolism, Tumor Necrosis Factor-alpha metabolism
Abstract

FADD/MORT1 (The adaptor protein of Fas Associate Death Domain/Mediator of Receptor Induced Toxicity) is essential for signal transduction of death receptor signaling. We have previously shown that FADD is significantly up-regulated in TNFalpha/ActD induced apoptosis. Over-expression of FADD also induces death of lung cancer cells and primary hepatocytes. We hypothesize that the increase in detectable FADD levels require the proximal steps in apoptotic signaling and speculated that FADD would be redistributed in cells destined to undergo apoptosis. We show that monomeric non-phosphorylated FADD is up-regulated in hepatocytes treated with TNFalpha/ActD and that it accumulates in the cytoplasm. Nuclear phosphorylated FADD decreases with TNFalpha/ActD treatment. Dimeric FADD in the cytoplasm remains constant with TNFalpha/ActD. The change in FADD levels and distribution was dependent on caspase-3, caspase-8 activity and the presence of BID. Thus, changes in FADD levels and distribution are downstream of caspase activation and mitochondria changes that are initiated by the formation of the DISC complex. Changes in FADD levels and distribution may represent a novel feed-forward mechanism to propagate apoptosis signaling in hepatocytes.

Published
2008
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