Mutational Effects on Thermostable Superoxide Dismutase from Aquifex pyrophilus: Understanding the Molecular Basis of Protein Thermostability

2001 ◽  
Vol 288 (1) ◽  
pp. 263-268 ◽  
Author(s):  
Jae-Hwan Lim ◽  
Kwang Yeon Hwang ◽  
Juhyun Choi ◽  
Duck Yeon Lee ◽  
Byung-Yoon Ahn ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Molecular Basis ◽  
Protein Thermostability ◽  
Aquifex Pyrophilus

Neocytolysis Is Associated with Changes in Increase of Mitochondrial Content and Impaired Protection From Reactive Oxygen Species

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1029-1029
Author(s):  
Jihyun Song ◽  
Donghoon Yoon ◽  
Perumal Thiagarajan ◽  
Josef T. Prchal
Keyword(s):  
Reactive Oxygen Species ◽  
Superoxide Dismutase ◽  
Transcription Factor ◽  
Blood Cells ◽  
Molecular Basis ◽  
Reticulocyte Count ◽  
Reactive Oxygen ◽  
P Value ◽  
Oxygen Species ◽  
Mitochondrial Content

Abstract Abstract 1029 Red blood cells (RBCs) continuously transport large amount of oxygen over their life time and require precise mechanism to protect themselves from oxidative stress. RBCs cannot respond to rapid oxygen changes by synthesizing enzymes and other proteins. Chronic hypoxia enhances erythropoiesis with ensuing polycythemia. With return to normoxia, red cell mass is reduced by neocytolysis, characterized by selective hemolysis of the young RBCs. Neocytolysis was described in astronauts, in those descending from high-altitude, and in newborn babies leaving hypoxic environment of uterus. While it has been suggested that neocytolysis is caused by very low erythropoietin levels, its molecular basis remains obscure. However, we argue against this postulate since RBCs lack pathway for erythropoietin signaling. We hypothesize that rapid changes of hypoxia-regulated hypoxia-inducible transcription factors (HIFs) regulated genes (other than erythropoietin) may be responsible, one such a gene (BNIP3L/NIX) regulates mitochondrial autophagy. Upon normoxic return young RBCs generated in hypoxia cannot cope because of decreased levels of oxidant protecting defenses regulated by HIF-dependent FOXO3a transcription factor. In order to test this hypothesis, we created an animal model depicted in Figure 1. We placed C57/BL6 mice in a hypoxia chamber at 12 % O2, (equivalent to 4500 m of altitude) for 10 days and then returned them to a normoxic condition. We measured hematocrit levels and reticulocyte count before and after hypoxia treatment.Fig. 1Hematocrit level and reticulocyte count before hypoxia and post hypoxiaFig. 1. Hematocrit level and reticulocyte count before hypoxia and post hypoxia Legend: BH: Before Hypoxia, PH: Post Hypoxia *; P value ≤ 0.05, **; P value ≤0.01, ***; P value ≤0.001, P value calculated using student T test comparing values before hypoxia. Epo levels increased 1.6 fold during hypoxia and then reduced up to undetectable level at PH day 4. Then Epo gradually increased to ∼3 fold during PH day 10∼28. During PH day 10∼21, the mice became anemic, even though Epo and reticulocytes remained high. These results suggest that neocytolysis occurs after several days of exposure to normoxia and it is not caused by Epo mechanism. To investigate the molecular basis of the observed neocytolysis in this mouse model, we measured the mitochondrial content in reticulocytes, anti-oxidative enzyme activities (glutathione peroxidase and reductase, catalase, and superoxide dismutase) that scavenge reactive oxygen species in RBCs, possibly coexistent with up-regulation of mitochondrial content upon normoxic return. Reticulocytes at returning normoxia generated more mitochondria several days after normoxic return, In contrast catalase activity was reduced during hypoxia and at PH day 4, but by PH day 10 its activity increased, and the catalase activity decrease coincided with a decrease in hematocrit. To investigate whether hypoxia drives neocytolysis under our conditions, we tested 2 known HIF target genes, Bnip3L (also called Nix), a pro-apoptotic protein that causes mitochondrial autophagy. Bnip3L mRNA was induced 9x during hypoxia and reduced 2x at PH day 6, compared to before hypoxia. We also analyzed Foxo3a, a transcription factor, in sorted reticulocytes (CD71+/TER119+/Mitochondria+) which regulates cellular stress responses such as catalase and superoxide dismutase (SOD). Foxo3a was slightly increased during hypoxia and reduced 4x at PH day 6 from levels before hypoxia. In conclusion, we developed mouse model to study neocytolysis. Our data suggest that increased mitochondria retained by Bnip3L repression leads to an accumulation of reactive oxygen species (whether in reticulocytes, platelets or leukocytes), and that young RBCs formed in hypoxia with insufficient antioxidant enzyme activity cannot survive because of excessive reactive oxygen species, with ensuing hemolysis. Studies of the role of other blood cells, as well as human studies of mountain climbers upon their return to sea level, are in progress. Disclosures: No relevant conflicts of interest to declare.

Exploring the molecular basis of human manganese superoxide dismutase inactivation mediated by tyrosine 34 nitration

2011 ◽  
Vol 507 (2) ◽  
pp. 304-309 ◽  
Author(s):  
Diego M. Moreno ◽  
Marcelo A. Martí ◽  
Pablo M. De Biase ◽  
Darío A. Estrin ◽  
Verónica Demicheli ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Molecular Basis ◽  
Manganese Superoxide Dismutase ◽  
Manganese Superoxide

The crystal structure of an Fe-superoxide dismutase from the hyperthermophile Aquifex pyrophilus at 1.9 å resolution: structural basis for thermostability

1997 ◽  
Vol 270 (2) ◽  
pp. 259-274 ◽  
Author(s):  
Jae-Hwan Lim ◽  
Yeon Gyu Yu ◽  
Ye Sun Han ◽  
Seung-je Cho ◽  
Byung-Yoon Ahn ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Superoxide Dismutase ◽  
Structural Basis ◽  
Aquifex Pyrophilus

Mechanisms of molluscan host resistance and of parasite strategies for survival

Parasitology ◽  
2001 ◽  
Vol 123 (7) ◽  
pp. 159-167 ◽  
Author(s):  
C. J. BAYNE ◽  
U. K. HAHN ◽  
R. C. BENDER
Keyword(s):  
Nitric Oxide ◽  
Hydrogen Peroxide ◽  
Superoxide Dismutase ◽  
Host Resistance ◽  
Respiratory Burst ◽  
Molecular Basis ◽  
Metabolic Intermediates ◽  
The Past ◽  
Critical Components ◽  
Oxide Synthase

In parallel with massive research efforts in human schistosomiasis over the past 30 years, persistent efforts have been made to understand the basis for compatibility and incompatibility in molluscan schistosomiasis. Snail plasma contains molecules that are toxic to trematodes, but these seem to kill only species that never parasitize the mollusc used as the source of plasma. A sporocyst will be killed actively by haemocytes alone if they are from a snail that is resistant to the trematode. Oxygen-dependent killing mechanisms play a major role. Enzymes such as NADPH oxidase, superoxide dismutase, myeloperoxidase and nitric oxide synthase are critical components of the putative killing pathways. Metabolic intermediates such as hydrogen peroxide and nitric oxide appear to be more important against trematodes than the shorter-lived intermediates that are more important in anti-microbial defences. Products secreted by trematode larvae influence the physiology of snail haemocytes, implying active counter-defences mounted by the parasite, but these remain largely unexplored. A possible molecular basis for the susceptibility/resistance dichotomy in molluscan schistosomiasis is suggested to be deficient forms of enzymes in the respiratory burst pathway, and a selective disadvantage for schistosome resistance is an integral component of this model.

Molecular basis for tumor necrosis factor-induced increase in pulmonary superoxide dismutase activities

1990 ◽  
Vol 259 (6) ◽  
pp. L506-L512 ◽  
Author(s):  
M. F. Tsan ◽  
J. E. White ◽  
C. Treanor ◽  
J. B. Shaffer
Keyword(s):  
Superoxide Dismutase ◽  
Enzyme Activity ◽  
Tumor Necrosis Factor ◽  
Molecular Basis ◽  
Tumor Necrosis ◽  
Oxygen Toxicity ◽  
Specific Protein ◽  
Antioxidant Enzyme Activities ◽  
Tracheal Insufflation ◽  
Necrosis Factor

Tracheal insufflation of tumor necrosis factor (TNF) enhances pulmonary antioxidant enzyme activities and protects rats against oxygen toxicity (J. Appl. Physiol. 68: 1211–1219, 1990). We now report that tracheal insufflation of TNF selectively induced pulmonary Mn-superoxide dismutase (SOD) mRNA in normoxia- and hyperoxia-exposed rats, leading to increased amounts of Mn-SOD specific protein and enzyme activity. Tracheal insufflation of TNF had no effect on the levels of pulmonary Cu,Zn-SOD mRNA or specific protein. Hyperoxia alone also selectively induced pulmonary Mn-SOD mRNA. However, the hyperoxia-induced increase in Mn-SOD mRNA was not associated with an increase in Mn-SOD specific protein or enzyme activity. The results suggest that the increased pulmonary Mn-SOD in TNF-insufflated rats may contribute to the TNF-induced protection against oxygen toxicity.

Renilla Bioluminescence: A Morphologic Approach to the Location of Photocytes

1974 ◽  
Vol 32 ◽  
pp. 208-209
Author(s):  
Ben O. Spurlock ◽  
Milton J. Cormier
Keyword(s):  
Excited State ◽  
Ground State ◽  
Molecular Basis ◽  
Light Emission ◽  
Chemical Basis ◽  
Electronic Excited State ◽  
Colonial Form ◽  
The Common ◽  
Eighteenth And Nineteenth Centuries ◽  
Catalyzed Oxidation

The phenomenon of bioluminescence has fascinated layman and scientist alike for many centuries. During the eighteenth and nineteenth centuries a number of observations were reported on the physiology of bioluminescence in Renilla, the common sea pansy. More recently biochemists have directed their attention to the molecular basis of luminosity in this colonial form. These studies have centered primarily on defining the chemical basis for bioluminescence and its control. It is now established that bioluminescence in Renilla arises due to the luciferase-catalyzed oxidation of luciferin. This results in the creation of a product (oxyluciferin) in an electronic excited state. The transition of oxyluciferin from its excited state to the ground state leads to light emission.

Androgen-induced plasticity at a “vocal” neuromuscular synapse

1994 ◽  
Vol 52 ◽  
pp. 32-33
Author(s):  
Darcy B. Kelley ◽  
Martha L. Tobias ◽  
Mark Ellisman
Keyword(s):  
Xenopus Laevis ◽  
Motor Neurons ◽  
Sexual Differentiation ◽  
Molecular Basis ◽  
Neuromuscular Synapse ◽  
Sexually Dimorphic ◽  
Intracellular Protein ◽  
Developmental Program ◽  
Androgen Action ◽  
Clawed Frog

Brain and muscle are sexually differentiated tissues in which masculinization is controlled by the secretion of androgens from the testes. Sensitivity to androgen is conferred by the expression of an intracellular protein, the androgen receptor. A central problem of sexual differentiation is thus to understand the cellular and molecular basis of androgen action. We do not understand how hormone occupancy of a receptor translates into an alteration in the developmental program of the target cell. Our studies on sexual differentiation of brain and muscle in Xenopus laevis are designed to explore the molecular basis of androgen induced sexual differentiation by examining how this hormone controls the masculinization of brain and muscle targets.Our approach to this problem has focused on a highly androgen sensitive, sexually dimorphic neuromuscular system: laryngeal muscles and motor neurons of the clawed frog, Xenopus laevis. We have been studying sex differences at a synapse, the laryngeal neuromuscular junction, which mediates sexually dimorphic vocal behavior in Xenopus laevis frogs.

A molecular basis for opiate action

1998 ◽  
Vol 33 ◽  
pp. 65-77 ◽  
Author(s):  
Dominique Massotte ◽  
Brigitte L. Kieffer
Keyword(s):  
Molecular Basis
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