Germline-soma Supply Mitochondria for mtDNA Inheritance in Mouse Oogenesis

Maternal transmission paradigm of mtDNA remains controversial in mammalian oogenesis. Germline-soma-to-oocyte communication by numerous transzonal nanotubes (TZTs) reminds whether intercellular mitochondrial transfer is associated with maternal inheritance. Here, we found that mouse oocytes egocentrically receive mitochondria via TZTs, which projected from germline-soma, to achieve 105 copies, instead of de novo synthesis of mtDNA subpopulation in growing oocytes. De novo assembled TZTs amongst germline-soma and oocytes accumulated mtDNA amounts of the oocytes in vitro. However, mitochondrial supplement from germline-soma gradually diminished along with oocyte growth and was terminated by meiosis resumption, in line with a decrease in the proportion of germline-soma with thriving mtDNA replication and FSH capture capability. Thus, germline-soma-to-oocyte mitochondrial transfer is responsible for mammalian mtDNA inheritance as well as oogenesis and aging.

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Bioactive Alkaloids from the Tropical Marine Sponge Axinella carteri

Zeitschrift für Naturforschung C ◽

10.1515/znc-1995-9-1012 ◽

1995 ◽

Vol 50 (9-10) ◽

pp. 669-674 ◽

Cited By ~ 35

Author(s):

A. Supriyono ◽

B. Schwarz ◽

V. Wray ◽

L. Witte ◽

W. E. G. Müller ◽

...

Keyword(s):

Marine Sponge ◽

Insecticidal Activity ◽

De Novo ◽

The Philippines ◽

De Novo Synthesis ◽

Mouse Lymphoma Cells ◽

Guanidine Alkaloids ◽

Neonate Larvae ◽

Mouse Lymphoma

Abstract Analysis of the tropical marine sponge Axinella carteri afforded six unusual alkaloids, including the new brominated guanidine derivative 3-bromo-hymenialdisine. The structure elucidation of the new alkaloid is described. The alkaloid patterns of sponges collected in Indonesia or in the Philippines were shown to be qualitatively identical suggesting de novo synthesis by the sponge or by endosymbiontic microorganisms rather than uptake by filterfeeding. All alkaloids were screened for insecticidal activity as well as for cytotoxicity. The guanidine alkaloids hymenialdisine and debromohymenialdisine exhibited insecticidal activity towards neonate larvae of the polyphagous pest insect Spodoptera littoralis (LD50s of 88 and 125 ppm, respectively), when incorporated into artificial diet and offered to the larvae in a chronic feeding bioassay. The remaining alkaloids, including the new compound, were inactive in this bioassay. Cytotoxicity was studied in vitro using L5178y mouse lymphoma cells. Debromohymenialdisine was again the most active compound (ED50 1.8 μg/ml) followed by hymenialdisine and 3-bromohymenialdisine, which were essentially equitoxic and exhibited ED50s of 3.9 μg/ml in both cases. The remaining alkaloids were inactive against this cell line

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Immunology: Evidence for the in-vitro de-novo synthesis of immunoglobulin and a previously undescribed 17 kDa protein (TEP-2) by the mucosa of the Fallopian tube

Human Reproduction ◽

10.1093/oxfordjournals.humrep.a138228 ◽

1993 ◽

Vol 8 (8) ◽

pp. 1199-1202 ◽

Cited By ~ 4

Author(s):

S.D. Maguiness ◽

K. Shrimanker ◽

O. Djahanbakhch ◽

B. Teisner ◽

J.G. Grudzinskas

Keyword(s):

Fallopian Tube ◽

De Novo ◽

De Novo Synthesis

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Differential cytolocalization of prosomes in axolotl during oogenesis and meiotic maturation

Journal of Cell Science ◽

10.1242/jcs.90.4.543 ◽

1988 ◽

Vol 90 (4) ◽

pp. 543-553 ◽

Cited By ~ 1

Author(s):

J. Gautier ◽

J.K. Pal ◽

M.F. Grossi de Sa ◽

J.C. Beetschen ◽

K. Scherrer

Keyword(s):

Mammalian Cells ◽

De Novo ◽

Germinal Vesicle ◽

Immunoblot Analysis ◽

Ambystoma Mexicanum ◽

Meiotic Maturation ◽

Crescent Formation ◽

Oocyte Growth ◽

Oocyte Cytoplasm

The prosomes, a novel type of small RNA-protein complex previously characterized in avian and mammalian cells, were isolated from axolotl (Ambystoma mexicanum) oocytes and identified by sedimentation analysis and protein composition. The prosomal nature of these particles was further ascertained by immunoblot analysis with anti-duck prosome monoclonal antibodies. By in vitro [35S]methionine labelling, de novo synthesis of prosomal proteins could be detected neither during oogenesis nor meiotic maturation. The results obtained by both indirect immunofluorescence and immunoblot analyses demonstrated a dramatic change in the localization of prosomal antigens during oocyte development. They were initially detected in the oocyte cytoplasm, during oocyte growth. At the end of vitellogenesis (stages V-VI), they entered the nucleus (germinal vesicle) and were accumulated there to the highest concentration. During oocyte maturation, after nuclear envelope breakdown, prosomal antigens were found to be localized again in the cytoplasm, until fertilization. No specific localization of prosomal antigens in mature oocytes, unfertilized and fertilized eggs was observed within the oocyte cytoplasm in relation to the cytoplasmic rearrangements leading to grey crescent formation.

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Release of interleukin-1 and interleukin-6 from human monocytes by antithymocyte globulin: requirement for de novo synthesis

Blood ◽

10.1182/blood.v80.10.2531.2531 ◽

1992 ◽

Vol 80 (10) ◽

pp. 2531-2538 ◽

Cited By ~ 17

Author(s):

P Rameshwar ◽

P Gascon

Keyword(s):

Antithymocyte Globulin ◽

De Novo ◽

Interleukin 1 ◽

Immunosuppressive Agent ◽

Biologically Active ◽

Human Monocytes ◽

Blood Monocytes ◽

De Novo Synthesis ◽

Hematopoietic Growth Factors

Abstract Antithymocyte globulin (ATG) is an effective treatment in patients with severe aplastic anemia (SAA). Its mechanism of action remains unclear, although it has been assumed to be immunosuppressive. However, ATG has also been shown by several laboratories to be immunostimulatory. Recently, interleukin-1 (IL-1) production has been found to be decreased in lipopolysaccharide-stimulated peripheral blood monocytes obtained from SAA patients. We have investigated the ability of ATG to function as an immunostimulatory agent via the production of IL-1 and IL-6 by normal human monocytes in vitro. Supernatants from ATG- stimulated monocytes were assayed for biologically active and immunoreactive IL-1 and IL-6. We have found that ATG, via its F(ab')2 fragment is a powerful inducer of IL-1 and IL-6 production. Furthermore, ATG induction of both cytokines from normal monocytes required de novo synthesis, as determined by 35S-methionine incorporation. Because these two cytokines synergize with other cytokines at both the stem cell and progenitor levels, these stimulatory properties of ATG may be relevant to the treatment of SAA. This would favor the hypothesis of a bimodal mechanism for ATG as an inducer of hematopoietic growth factors and as an immunosuppressive agent.

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Apoptosis in megaloblastic anemia occurs during DNA synthesis by a p53-independent, nucleoside-reversible mechanism

Blood ◽

10.1182/blood.v96.9.3249 ◽

2000 ◽

Vol 96 (9) ◽

pp. 3249-3255 ◽

Cited By ~ 46

Author(s):

Mark J. Koury ◽

James O. Price ◽

Geoffrey G. Hicks

Keyword(s):

Dna Synthesis ◽

De Novo ◽

Megaloblastic Anemia ◽

Experimental Studies ◽

Hematopoietic Cells ◽

S Phase ◽

De Novo Synthesis ◽

Complete Reversal ◽

Phase Accumulation

Abstract Deficiency of folate or vitamin B12 (cobalamin) causes megaloblastic anemia, a disease characterized by pancytopenia due to the excessive apoptosis of hematopoietic progenitor cells. Clinical and experimental studies of megaloblastic anemia have demonstrated an impairment of DNA synthesis and repair in hematopoietic cells that is manifested by an increased percentage of cells in the DNA synthesis phase (S phase) of the cell cycle, compared with normal hematopoietic cells. Both folate and cobalamin are required for normal de novo synthesis of thymidylate and purines. However, previous studies of impaired DNA synthesis and repair in megaloblastic anemia have concerned mainly the decreased intracellular levels of thymidylate and its effects on nucleotide pools and misincorporation of uracil into DNA. An in vitro model of folate-deficient erythropoiesis was used to study the relationship between the S-phase accumulation and apoptosis in megaloblastic anemia. The results indicate that folate-deficient erythroblasts accumulate in and undergo apoptosis in the S phase when compared with control erythroblasts. Both the S-phase accumulation and the apoptosis were induced by folate deficiency in erythroblasts fromp53 null mice. The complete reversal of the S-phase accumulation and apoptosis in folate-deficient erythroblasts required the exogenous provision of specific purines or purine nucleosides as well as thymidine. These results indicate that decreased de novo synthesis of purines plays as important a role as decreased de novo synthesis of thymidylate in the pathogenesis of megaloblastic anemia.

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PDGF and IL-1 induce and activate specific protein kinase C isoforms in mesangial cells

AJP Renal Physiology ◽

10.1152/ajprenal.1996.271.1.f108 ◽

1996 ◽

Vol 271 (1) ◽

pp. F108-F113 ◽

Cited By ~ 6

Author(s):

M. B. Ganz ◽

B. Saksa ◽

R. Saxena ◽

K. Hawkins ◽

J. R. Sedor

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

De Novo ◽

Mesangial Cells ◽

De Novo Synthesis ◽

Kinase C ◽

Pkc Isoforms ◽

Alpha Beta ◽

Pkc Alpha

In vitro and in vivo data suggest a remarkable plasticity in the differentiated phenotype of intrinsic glomerular cells, which after injury express new structures and functions. We have shown that a protein kinase C (PKC) isoform, beta II, is expressed in diseased but not normal glomeruli. Since intrarenal cytokine synthesis has been implicated in the pathogenesis of progressive glomerular injury, we have hypothesized that these mediators induce a change in isoform profile. To test this hypothesis in vitro, we have determined whether platelet-derived growth factor (PDGF) and interleukin-1 (IL-1) alter the expression or activation of PKC isoforms in cultured mesangial cells (MCs). By immunoblot and ribonuclease (RNase) protection assays, both PDGF and IL-1 induce as early as 2 h de novo synthesis of PKC-beta II. Since MCs constitutively express PKC-alpha, -beta I, and -zeta, we also determined whether IL-1 or PDGF alter the activity of these isoforms. PDGF maximally induced translocation of PKC-alpha (10 min), -beta I (90 min), -epsilon (120 min), and -zeta (120 min) from the cytosolic to the membrane fraction. IL-1, in contrast, did not alter the distribution of alpha, beta I, or epsilon at any time measured but did induce PKC-zeta translocation. These data suggest inflammatory mediators regulate PKC isoform activity in diseased glomeruli both by de novo synthesis of unexpressed isoforms and by activation of constitutively expressed PKC isoforms.

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NAD+-Dependent Deacetylase Hst1p Controls Biosynthesis and Cellular NAD+ Levels in Saccharomyces cerevisiae

Molecular and Cellular Biology ◽

10.1128/mcb.23.19.7044-7054.2003 ◽

2003 ◽

Vol 23 (19) ◽

pp. 7044-7054 ◽

Cited By ~ 97

Author(s):

Antonio Bedalov ◽

Maki Hirao ◽

Jeffrey Posakony ◽

Melisa Nelson ◽

Julian A. Simon

Keyword(s):

De Novo ◽

Critical Role ◽

Salvage Pathway ◽

De Novo Synthesis ◽

Array Analysis ◽

Binding Partner ◽

Dependent Protein ◽

New Protein

ABSTRACT Nicotine adenine dinucleotide (NAD+) performs key roles in electron transport reactions, as a substrate for poly(ADP-ribose) polymerase and NAD+-dependent protein deacetylases. In the latter two processes, NAD+ is consumed and converted to ADP-ribose and nicotinamide. NAD+ levels can be maintained by regeneration of NAD+ from nicotinamide via a salvage pathway or by de novo synthesis of NAD+ from tryptophan. Both pathways are conserved from yeast to humans. We describe a critical role of the NAD+-dependent deacetylase Hst1p as a sensor of NAD+ levels and regulator of NAD+ biosynthesis. Using transcript arrays, we show that low NAD+ states specifically induce the de novo NAD+ biosynthesis genes while the genes in the salvage pathway remain unaffected. The NAD+-dependent deacetylase activity of Hst1p represses de novo NAD+ biosynthesis genes in the absence of new protein synthesis, suggesting a direct effect. The known Hst1p binding partner, Sum1p, is present at promoters of highly inducible NAD+ biosynthesis genes. The removal of HST1-mediated repression of the NAD+ de novo biosynthesis pathway leads to increased cellular NAD+ levels. Transcript array analysis shows that reduction in cellular NAD+ levels preferentially affects Hst1p-regulated genes in comparison to genes regulated with other NAD+-dependent deacetylases (Sir2p, Hst2p, Hst3p, and Hst4p). In vitro experiments demonstrate that Hst1p has relatively low affinity toward NAD+ in comparison to other NAD+-dependent enzymes. These findings suggest that Hst1p serves as a cellular NAD+ sensor that monitors and regulates cellular NAD+ levels.

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