scholarly journals Naja naja oxiana Cobra Venom Cytotoxins CTI and CTII Disrupt Mitochondrial Membrane Integrity: Implications for Basic Three-Fingered Cytotoxins

PLoS ONE ◽  
2015 ◽  
Vol 10 (6) ◽  
pp. e0129248 ◽  
Author(s):  
Sardar E. Gasanov ◽  
Indira H. Shrivastava ◽  
Firuz S. Israilov ◽  
Aleksandr A. Kim ◽  
Kamila A. Rylova ◽  
...  
Keyword(s):  
Mitochondrial Membrane ◽  
Membrane Integrity ◽  
Cobra Venom ◽  
Naja Naja

scholarly journals Cardiotoxin II from Taiwan cobra venom, Naja naja atra. Structure in solution and comparison among homologous cardiotoxins.

1994 ◽  
Vol 269 (38) ◽  
pp. 23500-23508
Author(s):  
R. Bhaskaran ◽  
C.C. Huang ◽  
Y.C. Tsai ◽  
G. Jayaraman ◽  
D.K. Chang ◽  
...  
Keyword(s):  
Cobra Venom ◽  
Naja Naja ◽  
Structure In Solution ◽  
Naja Atra ◽  
Cardiotoxin Ii

Vitamin E prevents hypobaric hypoxia-induced mitochondrial dysfunction in skeletal muscle

2007 ◽  
Vol 113 (12) ◽  
pp. 459-466 ◽  
Author(s):  
José Magalhães ◽  
Rita Ferreira ◽  
Maria J. Neuparth ◽  
Paulo J. Oliveira ◽  
Franklim Marques ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Vitamin E ◽  
Mitochondrial Dysfunction ◽  
Hypobaric Hypoxia ◽  
Mitochondrial Membrane ◽  
Mitochondrial Protein ◽  
Membrane Integrity ◽  
Outer Mitochondrial Membrane ◽  
Hypoxia Exposure

In the present study, the effect of vitamin E (α-tocopherol) on mice skeletal muscle mitochondrial dysfunction and oxidative damage induced by an in vivo acute and severe hypobaric hypoxic insult (48 h at a barometric pressure equivalent to 8500 m) has been investigated. Male mice (n=24) were randomly divided into the following four groups (n=6): control (C), hypoxia (H), vitamin E (VE; 60 mg/kg of body weight intraperitoneally, three times/week for 3 weeks) and hypoxia+VE (HVE). A significant increase in mitochondrial protein CGs (carbonyl groups) was found in the H group compared with the C group. Confirming previous observations from our group, hypoxia induced mitochondrial dysfunction, as identified by altered respiratory parameters. Hypoxia exposure increased Bax content and decreased the Bcl-2/Bax ratio, whereas Bcl-2 remained unchanged. Inner and outer mitochondrial membrane integrity were significantly affected by hypoxia exposure; however, vitamin E treatment attenuated the effect of hypoxia on mitochondrial oxidative phosphorylation and on the levels of CGs. Vitamin E supplementation also prevented the Bax and Bcl-2/Bax ratio impairments caused by hypoxia, as well as the decrease in inner and outer mitochondrial membrane integrity. In conclusion, the results suggest that vitamin E prevents the loss of mitochondrial integrity and function, as well as the increase in Bax content, which suggests that mitochondria are involved in increased cell death induced by severe hypobaric hypoxia in mice skeletal muscle.

scholarly journals CBMT-17. DEFECTIVE QKI-DEPENDENT LIPID METABOLISM INDUCES GENOMIC INSTABILITY AND SENSITIZES GLIOBLASTOMA TO IMMUNOTHERAPY

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi36-vi36
Author(s):  
Takashi Shingu ◽  
Jian Hu
Keyword(s):  
Genomic Instability ◽  
Mitochondrial Membrane ◽  
Rna Binding ◽  
Cytoplasmic Membrane ◽  
Unsaturated Fatty Acids ◽  
Rna Stability ◽  
Membrane Integrity ◽  
Immune Checkpoints ◽  
Mitochondrial Defects ◽  
And Function

Abstract Despite transformative effects on the therapy of cancers such as melanoma and lung adenocarcinoma, blockade of the T cell immune checkpoints has generated limited impact on glioblastoma. Identifying genetic/genomic alterations that could potentially sensitize the patients to immunotherapy will significantly improve the efficacy of immunotherapy on glioblastoma patients. As part of our effort to identify novel glioma suppressors that affect the interaction of GSCs with their microenvironment, we discovered that the RNA-binding protein Quaking (QKI) is a key regulator of cellular endocytosis. QKI is mutated or deleted in ~34% of human glioblastomas. Supporting QKI’s tumor suppresser function, 92% of the Nestin-CreERT2;QkiL/L;PtenL/L;p53L/L mice developed glioblastoma with a median survival of 105 days, however, the Nestin-CreERT2;PtenL/L;p53L/L mice did not develop any glioma up to a year. Mechanistically, QKI regulates the RNA stability and alternative splicing of numerous protein and lipid components of endolysosomes, particularly the unsaturated fatty acids (UFAs). Functionally, deletion of Qki and inhibition of UFA biosynthesis both decrease endolysosome-mediated receptor degradation, thereby enriching receptors on the cytoplasmic membrane (e.g., Frizzled and Notch1) that are essential for maintaining stemness. This enrichment of receptor signaling enables GSCs to cope with the low ligand levels during their invasion. On the other hand, lower lysosomal activity induced by Qki deletion and UFA loss led to defective mitophagy. We also found that insufficient UFAs in mitochondrial membrane significantly compromised mitochondrial membrane integrity and function. These two mechanisms concomitantly led to accumulation of damaged mitochondria and higher levels of reactive oxygen species (ROS), and consequently genomic instability. Lastly, we found that the higher level of genomic instability induced by Qki loss rendered cells more sensitive to anti-CTLA4 and anti-PD1 antibodies. Taken together, our data suggest that Qki/UFA loss-induced endolysosomal and mitochondrial defects promote gliomagenesis yet render cells vulnerabilities that could be harnessed for therapeutic purposes.

scholarly journals Integrity of the plasma membrane, the acrosomal membrane, and the mitochondrial membrane potential of sperm in Nelore bulls from puberty to sexual maturity

2016 ◽  
Vol 68 (3) ◽  
pp. 620-628 ◽  
Author(s):  
L.S.L.S. Reis ◽  
A.A. Ramos ◽  
A.S. Camargos ◽  
E. Oba
Keyword(s):  
Plasma Membrane ◽  
Mitochondrial Membrane ◽  
Sexual Maturity ◽  
Wave Motion ◽  
Membrane Integrity ◽  
Mitochondrial Potential ◽  
Plasma Membrane Integrity ◽  
Scrotal Circumference ◽  
Acrosomal Membrane ◽  
Sperm Membrane

ABSTRACT This study evaluated the plasma membrane integrity, acrosomal membrane integrity, and mitochondrial membrane potential of Nelore bull sperm from early puberty to early sexual maturity and their associations with sperm motility and vigor, the mass motility of the spermatozoa (wave motion), scrotal circumference, and testosterone. Sixty Nelore bulls aged 18 to 19 months were divided into four lots (n=15 bulls/lot) and evaluated over 280 days. Semen samples, collected every 56 days by electroejaculation, were evaluated soon after collection for motility, vigor and wave motion under an optical microscope. Sperm membrane integrity, acrosomal integrity, and mitochondrial activity were evaluated under a fluorescent microscope using probe association (FITC-PSA, PI, JC-1, H342). The sperm were classified into eight integrity categories depending on whether they exhibited intact or damaged membranes, an intact or damaged acrosomal membrane, and high or low mitochondrial potential. The results show that bulls have a low amount of sperm with intact membranes at puberty, and the sperm show low motility, vigor, and wave motion; however, in bulls at early sexual maturity, the integrity of the sperm membrane increased significantly. The rate of sperm membrane damage was negatively correlated with motility, vigor, wave motion, and testosterone in the bulls, and a positive correlation existed between sperm plasma membrane integrity and scrotal circumference. The integrity of the acrosomal membrane was not influenced by puberty. During puberty and into early sexual maturity, bulls show low sperm mitochondrial potential, but when bulls reached sexual maturity, high membrane integrity with high mitochondrial potential was evident.

Sign in / Sign up

Export Citation Format

Share Document