scholarly journals Natural substances (acetogenins) from the family Annonaceae are powerful inhibitors of mitochondrial NADH dehydrogenase (Complex I)

1994 ◽  
Vol 301 (1) ◽  
pp. 161-167 ◽  
Author(s):  
M Degli Esposti ◽  
A Ghelli ◽  
M Ratta ◽  
D Cortes ◽  
E Estornell
Keyword(s):  
Complex I ◽  
Nadh Dehydrogenase ◽  
Potent Inhibitor ◽  
Submitochondrial Particles ◽  
Annonaceous Acetogenins ◽  
Natural Substances ◽  
Mammalian Mitochondria ◽  
The Family ◽  
Complex I Activity ◽  
First Time

Natural products from the plants of the family Annonaceae, collectively called Annonaceous acetogenins, are very potent inhibitors of the NADH-ubiquinone reductase (Complex I) activity of mammalian mitochondria. The properties of five of such acetogenins are compared with those of rotenone and piericidin, classical potent inhibitors of Complex I. Rolliniastatin-1 and rolliniastatin-2 are more powerful than piericidin in terms of both their inhibitory constant and the protein-dependence of their titre in bovine submitochondrial particles. These acetogenins could be considered therefore the most potent inhibitors of mammalian Complex I. Squamocin and otivarin also have an inhibitory constant lower than that of piericidin, but display a larger protein-dependence of the titre. Squamocin and otivarin, contrary to the other acetogenins, behave qualitatively like rotenone. Rolliniastatin-2 shows unique properties as its interaction, although mutually exclusive to that of piericidin, appears to be mutually non-exclusive to that of rotenone. It is the first time that a potent inhibitor of Complex I is found not to overlap the active site of rotenone.

scholarly journals Isoflurane Differentially Modulates Mitochondrial Reactive Oxygen Species Production via  Forward versus  Reverse Electron Transport Flow

2011 ◽  
Vol 115 (3) ◽  
pp. 531-540 ◽  
Author(s):  
Naoyuki Hirata ◽  
Yon Hee Shim ◽  
Danijel Pravdic ◽  
Nicole L. Lohr ◽  
Philip F. Pratt ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Electron Transport ◽  
Complex I ◽  
Ros Generation ◽  
Ros Production ◽  
Oxygen Species ◽  
Submitochondrial Particles ◽  
Anesthetic Preconditioning ◽  
Cardioprotective Effects ◽  
Complex I Activity

Background Reactive oxygen species (ROS) mediate the effects of anesthetic precondition to protect against ischemia and reperfusion injury, but the mechanisms of ROS generation remain unclear. In this study, the authors investigated if mitochondria-targeted antioxidant (mitotempol) abolishes the cardioprotective effects of anesthetic preconditioning. Further, the authors investigated the mechanism by which isoflurane alters ROS generation in isolated mitochondria and submitochondrial particles. Methods Rats were pretreated with 0.9% saline, 3.0 mg/kg mitotempol in the absence or presence of 30 min exposure to isoflurane. Myocardial infarction was induced by left anterior descending artery occlusion for 30 min followed by reperfusion for 2 h and infarct size measurements. Mitochondrial ROS production was determined spectrofluorometrically. The effect of isoflurane on enzymatic activity of mitochondrial respiratory complexes was also determined. Results Isoflurane reduced myocardial infarct size (40 ± 9% = mean ± SD) compared with control experiments (60 ± 4%). Mitotempol abolished the cardioprotective effects of anesthetic preconditioning (60 ± 9%). Isoflurane enhanced ROS generation in submitochondrial particles with nicotinamide adenine dinucleotide (reduced form), but not with succinate, as substrate. In intact mitochondria, isoflurane enhanced ROS production in the presence of rotenone, antimycin A, or ubiquinone when pyruvate and malate were substrates, but isoflurane attenuated ROS production when succinate was substrate. Mitochondrial respiratory experiments and electron transport chain complex assays revealed that isoflurane inhibited only complex I activity. Conclusions The results demonstrated that isoflurane produces ROS at complex I and III of the respiratory chain via the attenuation of complex I activity. The action on complex I decreases unfavorable reverse electron flow and ROS release in myocardium during reperfusion.

Metformin and respiratory chain complex I: the last piece of the puzzle?

2014 ◽  
Vol 463 (3) ◽  
pp. e3-e5 ◽  
Author(s):  
Eric Fontaine
Keyword(s):  
Complex I ◽  
Chain Complex ◽  
Recent Issue ◽  
Intact Cells ◽  
Biochemical Journal ◽  
The Difference ◽  
High Concentrations ◽  
Complex I Activity ◽  
First Time

Metformin is the most widely prescribed drug used to treat patients affected by Type 2 diabetes. Metformin has also been shown to prevent some forms of cell death; however, evidence suggests that it may have anti-neoplastic properties. All of these effects have been attributed to complex I inhibition, but the mechanism by which metformin leads to complex I inhibition is not fully understood. Although it has been reported that the incubation of functionally isolated complex I in the presence of high concentrations of metformin led to its inhibition, much lower concentrations of metformin have been shown to inhibit complex I in intact cells. In a recent issue of the Biochemical Journal, Bridges, Jones, Pollak and Hirst [(2014) Biochem. J. 462, 475–487] studied for the first time the effect of metformin on purified complex I. They report that millimolar concentrations of metformin directly inhibit complex I activity in a non-competitive manner. They also specify that the binding of metformin to complex I depends on its conformation. To explain the difference in concentration required to inhibit complex I in intact cells and on isolated enzyme, Bridges et al. (2014) propose that metformin concentrates within mitochondria in intact cells. Albeit theoretically plausible, this attractive hypothesis is not directly tested by Bridges et al. (2014) Moreover, although sparse, the current literature does not support this hypothesis.

Nitric oxide inhibits mitochondrial NADH:ubiquinone reductase activity through peroxynitrite formation

2001 ◽  
Vol 359 (1) ◽  
pp. 139-145 ◽  
Author(s):  
Natalia A. RIOBÓ ◽  
Emilio CLEMENTI ◽  
Mariana MELANI ◽  
Alberto BOVERIS ◽  
Enrique CADENAS ◽  
...  
Keyword(s):  
Complex I ◽  
Superoxide Radical ◽  
Reductase Activity ◽  
Complex Iii ◽  
Submitochondrial Particles ◽  
Nadh:Ubiquinone Reductase ◽  
Complex I Activity ◽  
State Concentration ◽  
The Brain

This study was aimed at assessing the effects of long-term exposure to NO of respiratory activities in mitochondria from different tissues (with different ubiquinol contents), under conditions that either promote or prevent the formation of peroxynitrite. Mitochondria and submitochondrial particles isolated from rat heart, liver and brain were exposed either to a steady-state concentration or to a bolus addition of NO. NO induced the mitochondrial production of superoxide anions, hydrogen peroxide and peroxynitrite, the latter shown by nitration of mitochondrial proteins. Long-term incubation of mitochondrial membranes with NO resulted in a persistent inhibition of NADH:cytochrome c reductase activity, interpreted as inhibition of NADH:ubiquinone reductase (Complex I) activity, whereas succinate:cytochrome c reductase activity, including Complex II and Complex III electron transfer, remained unaffected. This selective effect of NO and derived species was partially prevented by superoxide dismutase and uric acid. In addition, peroxynitrite mimicked the effect of NO, including tyrosine nitration of some Complex I proteins. These results seem to indicate that the inhibition of NADH:ubiquinone reductase (Complex I) activity depends on the NO-induced generation of superoxide radical and peroxynitrite and that Complex I is selectively sensitive to peroxynitrite. Inhibition of Complex I activity by peroxynitrite may have critical implications for energy supply in tissues such as the brain, whose mitochondrial function depends largely on the channelling of reducing equivalents through Complex I.

scholarly journals Lipid peroxidation and the reduction of ADP-Fe3+ chelate by NADH-ubiquinone reductase preparation from bovine heart mitochondria

1980 ◽  
Vol 192 (3) ◽  
pp. 861-866 ◽  
Author(s):  
K Takeshige ◽  
R Takayanagi ◽  
S Minakami
Keyword(s):  
Lipid Peroxidation ◽  
Complex I ◽  
Nadh Dehydrogenase ◽  
Reductase Activity ◽  
Thiol Group ◽  
Submitochondrial Particles ◽  
Essential Step ◽  
Sensitive Site ◽  
Mitochondrial Lipids ◽  
Optimal Ph

The NADH-ubiquinone reductase preparation (Complex I) of bovine hart mitochondria catalysed in the presence of reduced coenzymes and ADP-Fe3+ the lipid peroxidation of liposomes prepared from mitochondrial lipids. The apparent Km values for the coenzymes and the optimal pH of the reactions agreed well with those of the lipid peroxidation of the submitochondrial particles treated with rotenone. On assay of the reduction of ADP-Fe3+ chelate by the reduction of cytochrome c in the presence of superoxide dismutase and antimycin A or by the oxidation of reduced coenzymes, the reactions were not affected by rotenone but were inhibited by thiol-group inhibitors. The properties of the ADP-Fe3+ reductase activity were highly consistent with those of the lipid-peroxidation reaction. These observations suggest that electrons from reduced coenzymes are transferred to ADP-Fe3+ chelate from a component between a mercurial-sensitive site and the rotenone-sensitive one of the NADH dehydrogenase and that the reduction of ADP-Fe3+ chelate by the NADH dehydrogenase is an essential step in the lipid peroxidation.

scholarly journals The organization of NADH dehydrogenase polypeptides in the inner mitochondrial membrane

1980 ◽  
Vol 185 (2) ◽  
pp. 315-326 ◽  
Author(s):  
S Smith ◽  
C I Ragan
Keyword(s):  
Complex I ◽  
Mitochondrial Membrane ◽  
Nadh Dehydrogenase ◽  
Inner Mitochondrial Membrane ◽  
Submitochondrial Particles ◽  
Cytoplasmic Face ◽  
The Matrix

The organization of the constituent polypeptides of mitochondrial NADH dehydrogenase was studied by using two membrane-impermeable probes, diazobenzene[35S]sulphonate and lactoperoxidase-catalysed radioiodination. The incorporation of label into the subunits of the isolated enzyme was compared with that obtained with enzyme immunoprecipitated from labelled mitochondria or inverted submitochondrial particles. On the basis of accessibility to these two labels, we divide the polypeptides of Complex I into five groups: those that are apparently buried in the enzyme, those that are accessible to labelling in the isolated enzyme but not in the membrane, those that are exposed on the cytoplasmic face of the membrane, those that are exposed on the matrix face and finally those that are exposed on both faces and are therefore transmembranous. We conclude that NADH dehydrogenase is asymmetrically organized across the inner mitochondrial membrane.

Buried Narratives: Exhuming the Mother's Story in Oliver Twist

2018 ◽  
Vol 8 (3) ◽  
pp. 247-266
Author(s):  
Michelle L. Wilson
Keyword(s):  
Social Change ◽  
Maternal Inheritance ◽  
The Novel ◽  
Poor Law ◽  
The Family ◽  
The Law ◽  
First Time ◽  
Critical Consideration

Initially, Oliver Twist (1839) might seem representative of the archetypal male social plot, following an orphan and finding him a place by discovering the father and settling the boy within his inheritance. But Agnes Fleming haunts this narrative, undoing its neat, linear transmission. This reconsideration of maternal inheritance and plot in the novel occurs against the backdrop of legal and social change. I extend the critical consideration of the novel's relationship to the New Poor Law by thinking about its reflection on the bastardy clauses. And here, of course, is where the mother enters. Under the bastardy clauses, the responsibility for economic maintenance of bastard children was, for the first time, legally assigned to the mother, relieving the father of any and all obligation. Oliver Twist manages to critique the bastardy clauses for their release of the father, while simultaneously embracing the placement of the mother at the head of the family line. Both Oliver and the novel thus suggest that it is the mother's story that matters, her name through which we find our own. And by containing both plots – that of the father and the mother – Oliver Twist reveals the violence implicit in traditional modes of inheritance in the novel and under the law.

Faktor-Faktor Determinan yang melatar belakangi Kehamilan Remaja di Desa Pandansari Kecamatan Poncokusumo Kabupaten Malang

2020 ◽  
Vol 7 (2) ◽  
pp. 247-255
Author(s):  
Maria Magdalena Setyaningsih ◽  
Emy Sutiyarsih
Keyword(s):  
Sex Education ◽  
Teen Pregnancy ◽  
Teenage Pregnancy ◽  
Well Being ◽  
Case Control ◽  
Control Group ◽  
Case Group ◽  
The Family ◽  
History Of ◽  
First Time

Kehamilan remaja adalah kehamilan yang terjadi pada remaja berusia kurang dari 20 tahunan. Kehamilan remaja memberikan banyak kerugian bagi kesehatan, mental dan psikologis, kesejahteraan ekonomi dan peluang karier, kemiskinan dan prospek kehidupan masa depan remaja. Tujuan penelitian mengidentifikasi faktor determinan yang melatarbelakangi terjadinya kehamilan remaja. Jenis penelitian adalah penelitian analitik kategorik jenis survei kuantitatif dengan desain case control. Populasi semua perempuan yang bertempat tinggal di wilayah dusun Wonosari, Sukosari, dan Krajan Pandansari dan pernah/sedang hamil pertama kali pada usia kurang dari 20 tahun. Teknik pengambilan sampel cluster random sampling besar sampel 73. Berdasarkan hasil model akhir analisis multivariat, diketahui bahwa variabel pendidikan, riwayat kehamilan remaja pada keluarga dan usia menikah merupakan variabel yang berhubungan dengan kejadian kehamilan remaja setelah dikontrol oleh variabel akses informasi, responden berpendidikan rendah memiliki peluang 20,8 kali lebih tinggi, responden yang memiliki riwayat kehamilan remaja pada keluarga memiliki peluang 14,9 kali lebih tinggi, responden yang menikah pada usia <20 tahun memiliki peluang 12,1 kali lebih tinggi, responden dengan pemahaman yang kurang baik terkait penggunaan kondom memiliki peluang 5,9 kali lebih tinggi untuk terjadi kehamilan remaja. Oleh karena itu perlu dibangun karakter buiding, sosial karakter suport untuk para ibu remaja dan keluarga sehingga terbangun interaksi yang baik dalam keluarga yang dilandasi dengan pendidikan dan pemahaman yang baik tentang Pendidikan seksualitas. Teen pregnancy is a pregnancy that occurs in adolescents aged less than 20 years old. Teen pregnancy provides many disadvantages for health, mental, psychological, economic well-being, career opportunities, poverty, and the future life. The aim of the study was to identify the determinants underlying teen pregnancy incidence. This study was a quantitative study with categorical analytic method. The study design used a case control with two comparison groups. The groups were control group and case group. The population in this study was all women who lived in the Wonosari, Sukosari, and Krajan Pandansari district and had or were pregnant for the first time at the age of less than 20 years old. Seventy three respondents were recruited using cluster sampling technique. The case group consists of women who were or had pregnant for the first time at the age of less than 20 years old and their children are currently aged ≤ 1 years old. The control group consists of women who were pregnant for the first time at the age of > 20 years old. The data was collected using a questionnaire. The findings showed that education, history of teen pregnancy in family and the age of marriage were related to the incidence of teen pregnancy after being controlled by information access. Low-educated respondents had 20.8 times higher chance of experiencing teen pregnancy; respondents with a history of teen pregnancy in the family had 4.9 times higher chance of experiencing teen pregnancy; respondents who were married at the age of < 20 years old had 12.1 times higher chance of experiencing teen pregnancy; respondents with poor understanding of condom use had 5.9 times higher chance of teenage pregnancy. In conclusion, the findings suggest to build good interactions in the family based on education and a good understanding of sex education.

New records of some rare species in the family Hyaloscyphaceae (Ascomycota, Helotiales) from Central Russia

2013 ◽  
Vol 47 ◽  
pp. 135-142
Author(s):  
E. S. Popov
Keyword(s):  
Rare Species ◽  
New Records ◽  
Moscow Region ◽  
North Caucasus ◽  
Central Russia ◽  
The Family ◽  
First Time

Three rare species of discomycetes in the family Hyaloscyphaceae are reported from Central Russia (Oryol and Bryansk Regions). Proliferodiscus tricolor is recorded for the first time in Russia. Comments are made on Aeruginoscyphus sericeus and Eriopezia caesia previously reported only from Moscow Region and North Caucasus respectively.

Contribution to the flora of marine algae of the coastal zone of the northeastern part of the Sea of Okhotsk

2018 ◽  
Vol 52 (1) ◽  
pp. 63-73
Author(s):  
N. V. Evseeva
Keyword(s):  
Coastal Zone ◽  
Sea Of Okhotsk ◽  
Marine Algae ◽  
Herbarium Material ◽  
Northeastern Part ◽  
The Sea Of Okhotsk ◽  
The Family ◽  
First Time

The revision of the herbarium material, collected in the northern part of the Sea of Okhotsk in 1965–1966 and stored in VNIRO, allowed to expand the taxonomic list of macrophyte algae of the coastal zone of this area. The locations of discovery of 24 previously unmentioned species are described. Myrionema balticum, Ulvella repens, Syncoryne reinkei, Acrochaetium arcuatum were found in the Sea of Okhotsk for the first time. Most species new for the Sea of Okhotsk is represented by epiphytes of the family Ulvellaceae (Chlorophyta). The final taxonomic list of this region, including literature data, consists of 169 species.

New records of the true bugs (Heteroptera: Cimicomorpha, Pentatomomorpha) for the Northeast of European Russia

2014 ◽  
Vol 23 (2) ◽  
pp. 242-247
Author(s):  
A.N. Zinovjeva
Keyword(s):  
New Records ◽  
European Russia ◽  
True Bugs ◽  
The Family ◽  
First Time

Twenty seven species of the true bugs from the families Anthocoridae, Reduviidae, Miridae (Cimicomorpha), Coreidae, Thyreocoridae, Acanthosomatidae, and Pentatomidae (Pentatomomorpha) are recorded from the Northeast of European Russia for the first time. The family Thyreocoridae is for the first time reported from the region.

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