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141.
Ganesan LP Wei G Pengal RA Moldovan L Moldovan N Ostrowski MC Tridandapani S 《The Journal of biological chemistry》2004,279(52):54416-54425
Fc gamma receptor (Fc gamma R) clustering by immune complexes activates multiple signaling pathways leading to phagocytosis. We and others have previously reported that Akt is phosphorylated in response to Fc gamma R clustering. However, the functional consequence of Akt activation by Fc gamma R is not known. Using Raw 264.7 macrophage cells transfected to overexpress either constitutively active myristoylated (Myr)-Akt or a dominant-negative CAAX-Akt and bone marrow macrophages (BMMs) from wild-type and transgenic mice expressing macrophage-specific Myr-Akt, we analyzed the function of Akt in phagocytosis. We report that overexpression of Myr-Akt resulted in significant increase in phagocytic efficiency, whereas CAAX-Akt down-regulated phagocytosis in Raw 264.7 cells. Likewise BMMs expressing Myr-Akt displayed enhanced phagocytic ability. Analyzing the downstream effectors of Akt, we demonstrate that p70S6 kinase is constitutively phosphorylated in Myr-Akt-expressing BMMs. p70S6 kinase is reported to influence actin cytoskeleton and cell migration, suggesting that Akt may influence phagocytosis through the activation of p70S6 kinase. Consistent with this, overexpression of either wild-type or constitutively active but not a kinase-inactive p70S6 kinase in Raw 264.7 cells significantly enhanced phagocytosis. Likewise suppression of p70S6 kinase with rapamycin down-regulated phagocytic efficiency conferred by the expression of constitutively active Akt. These findings demonstrate a novel role for Akt in phagocytosis through the activation of p70S6 kinase. 相似文献
142.
Moldovan M Zagrean AM Avramescu S Savaran V Zagrean L 《Journal of cellular and molecular medicine》2004,8(1):135-140
During recovery after a transient global cerebral ischemia (TGCI), rat electrocorticogram (ECoG) shows epochs of synchronized activity (SA) alternating with epochs of low amplitude background activity (BA). The aim of this study was to compare the changes in these electrical activities during a 30-min recovery period that followed either a noninjuring (3 minutes, N=10) or an injuring (10 minutes, N=10) TGCI. During TGCI there was a 3 fold reduction in amplitudes of both SA and BA but no changes in frequency. During reperfusion following a 3 minutes TGCI, the amplitudes of both SA and BA recovered to about 70%. During the reperfusion that followed a 10 minutes TGCI, BA showed no recovery, whereas SA recovered to about 40%. During the 30 min reperfusion, there was a timedependent decrease in the frequency of SA, but independent on the duration of TGCI. In contrast, the frequency of the BA did not change during reperfusion. Our data indicate that following cerebral ischemia the recovery of SA can take place independently of BA. The lack of recovery in BA may indicate early subcortical neuronal damage. 相似文献
143.
Ventelä S Côme C Mäkelä JA Hobbs RM Mannermaa L Kallajoki M Chan EK Pandolfi PP Toppari J Westermarck J 《PloS one》2012,7(3):e33209
Protein phosphatase 2A (PP2A) is a critical regulator of protein serine/threonine phosphorylation. However, the physiological and developmental roles of different PP2A complexes are very poorly understood. Here, we show that a newly characterized PP2A inhibitory protein CIP2A is co-expressed with ki-67 and with self-renewal protein PLZF in the spermatogonial progenitor cell (SPC) population in the testis. CIP2A and PLZF expression was shown also to correlate Ki-67 expression in human testicular spermatogonia. Functionally, CIP2A mutant mouse testes exhibited smaller number of PLZF-positive SPCs and reduced sperm counts. Moreover, seminiferous tubuli cells isolated from CIP2A mutant mice showed reduced expression of Plzf and other renewal genes Oct-4 and Nanog at mRNA level. However, PLZF-deficient testes did not show altered CIP2A expression. Importantly, spermatogonia-specific restoration of CIP2A expression rescued PLZF expression and sperm production defects observed in CIP2A mutant mice. Taken together, these results reveal first physiological function for an emerging human oncoprotein CIP2A, and provide insights into maintenance of PLZF-positive progenitors. Moreover, demonstration that CIP2A expression can be systematically inhibited without severe consequences to normal mouse development and viability may have clinical relevance regarding targeting of oncogenic CIP2A for future cancer therapies. 相似文献
144.
Rivera LR Pontell L Cho HJ Castelucci P Thacker M Poole DP Frugier T Furness JB 《Cell and tissue research》2012,349(2):565-576
Recent investigation of the intestine following ischemia and reperfusion (I/R) has revealed that nitric oxide synthase (NOS) neurons are more strongly affected than other neuron types. This implies that NO originating from NOS neurons contributes to neuronal damage. However, there is also evidence of the neuroprotective effects of NO. In this study, we compared the effects of I/R on the intestines of neuronal NOS knockout (nNOS(-/-)) mice and wild-type mice. I/R caused histological damage to the mucosa and muscle and infiltration of neutrophils into the external muscle layers. Damage to the mucosa and muscle was more severe and greater infiltration by neutrophils occurred in the first 24?h in nNOS(-/-) mice. Immunohistochemistry for the contractile protein, α-smooth muscle actin, was used to evaluate muscle damage. Smooth muscle actin occurred in the majority of smooth muscle cells in the external musculature of normal mice but was absent from most cells and was reduced in the cytoplasm of other cells following I/R. The loss was greater in nNOS(-/-) mice. Basal contractile activity of the longitudinal muscle and contractile responses to nerve stimulation or a muscarinic agonist were reduced in regions subjected to I/R and the effects were greater in nNOS(-/-) mice. Reductions in responsiveness also occurred in regions of operated mice not subjected to I/R. This is attributed to post-operative ileus that is not significantly affected by knockout of nNOS. The results indicate that deleterious effects are greater in regions subjected to I/R in mice lacking nNOS compared with normal mice, implying that NO produced by nNOS has protective effects that outweigh any damaging effect of this free radical produced by enteric neurons. 相似文献
145.
Arakawa H Moldovan GL Saribasak H Saribasak NN Jentsch S Buerstedde JM 《PLoS biology》2006,4(11):e366
Proliferating cell nuclear antigen (PCNA) is a DNA polymerase cofactor and regulator of replication-linked functions. Upon DNA damage, yeast and vertebrate PCNA is modified at the conserved lysine K164 by ubiquitin, which mediates error-prone replication across lesions via translesion polymerases. We investigated the role of PCNA ubiquitination in variants of the DT40 B cell line that are mutant in K164 of PCNA or in Rad18, which is involved in PCNA ubiquitination. Remarkably, the PCNAK164R mutation not only renders cells sensitive to DNA-damaging agents, but also strongly reduces activation induced deaminase-dependent single-nucleotide substitutions in the immunoglobulin light-chain locus. This is the first evidence, to our knowledge, that vertebrates exploit the PCNA-ubiquitin pathway for immunoglobulin hypermutation, most likely through the recruitment of error-prone DNA polymerases. 相似文献
146.
Mette Romer Rosberg Susana Alvarez Christian Krarup Mihai Moldovan 《Neurochemical research》2013,38(6):1266-1277
Mice with a heterozygous knock-out of the myelin protein P0 gene (P0+/?) develop a neuropathy similar to human Charcot–Marie–Tooth disease. They are indistinguishable from wild-types (WT) at birth and develop a slowly progressing demyelinating neuropathy. The aim of this study was to investigate whether the regeneration capacity of early symptomatic P0+/? is impaired as compared to age matched WT. Right sciatic nerves were lesioned at the thigh in 7–8 months old mice. Tibial motor axons at ankle were investigated by conventional motor conduction studies and axon excitability studies using threshold tracking. To evaluate regeneration we monitored the recovery of motor function after crush, and then compared the fiber distribution by histology. The overall motor performance was investigated using Rotor-Rod. P0+/? had reduced compound motor action potential amplitudes and thinner myelinated axons with only a borderline impairment in conduction and Rotor-Rod. Plantar muscle reinnervation occurred within 21 days in all mice. Shortly after reinnervation the conduction of P0+/? regenerated axons was markedly slower than WT, however, this difference decayed with time. Nevertheless, after 1 month, regenerated P0+/? axons had longer strength-duration time constant, larger threshold changes during hyperpolarizing electrotonus and longer relative refractory period. Their performance at Rotor-Rod remained also markedly impaired. In contrast, the number and diameter distribution of regenerating myelinated fibers became similar to regenerated WT. Our data suggest that in the presence of heterozygously P0 deficient Schwann cells, regenerating motor axons retain their ability to reinnervate their targets and remyelinate, though their functional recovery is delayed. 相似文献
147.
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149.
Elena I. Oprita Lucia Moldovan Oana Craciunescu Otilia Zarnescu 《Central European Journal of Biology》2008,3(1):31-37
The purpose of the present study was to investigate the effect of a collagen/β-tricalcium phosphate (COL/β-TCP) composite
on osteoblast growth and proliferation. The COL/β-TCP composite was prepared by mixing COL type I with β-TCP, in 1:1 (w/w)
ratio and conditioned as sponge by freeze-drying. The osteoblast culture was obtained from rat calvaria bones by enzymatic
digestion and cells were seeded in the COL/β-TCP composite. The cell morphology and viability, alkaline phosphatase and osteocalcin,
as markers of osteoblast proliferation were evaluated at 3, 7 and 25 days of culture. Histological sections revealed that
cell colonization progressively increased inside the COL/β-TCP scaffold, and osteoblasts had a random distribution throughout
the scaffold. Cells cultured into the COL/β-TCP scaffold presented osteoblast phenotype, intense staining of alkaline phosphatase
and increased production of osteocalcin. Transmission electron micrographs revealed intimate contacts between osteoblasts
and the scaffold. MTT test indicated that the viability of the cells cultivated in the presence of COL/β-TCP scaffold was
similar to that of the control. All these results show that our COL/β-TCP composite act as a good substrate for rat osteoblast
proliferation and migration and could be a promising substitute for bone repair. 相似文献
150.