Sptrx-1, 2 and 3 are a series of thioredoxins specifically expressed in the testis/sperm. They play a significant role structurally and functionally in the process of spermiogenesis. The genesis and mutation of sptrx-1, 2 and 3 are correlated to male reproduction. Taking sptrx-1, 2 and 3 as the target of study and treatment will open up a new field in the clinical study of male reproduction.
Humans ; Male ; Mutation ; Spermatogenesis ; genetics ; physiology ; Spermatozoa ; chemistry ; cytology ; metabolism ; Testis ; chemistry ; cytology ; metabolism ; Thioredoxins ; biosynthesis ; genetics ; physiology

Thioredoxin (Trx) is a crucial protein for antioxidative defense, as well as a redox regulator of the intra- and extracellular signaling pathways and transcription factors. In this review, we focus on mammalian Trx and its association with Alzheimer's disease (AD) and Parkinson's disease (PD). Based on the evidence of neuroprotective effects of Trx, up-regulation of Trx may be a good strategy for prevention and treatment of AD and PD.
Alzheimer Disease ; metabolism ; Animals ; Antioxidants ; metabolism ; physiology ; Apoptosis ; drug effects ; Humans ; Neuroprotective Agents ; metabolism ; Oxidation-Reduction ; Parkinson Disease ; metabolism ; Thioredoxins ; metabolism ; physiology

Space flight is known to produce a number of neurological disturbances. The etiology is unknown, but it may involve increased oxidative stress. A line of experimental evidence indicates that space flight may disrupt antioxidant defense system and result in increased oxidative stress. In vitro studies found that abundant of NO was produced in rat pheochromocytoma (PC12) cells, SHSY5Y neuroblastoma cells, and protein nitration was increased in PC12 cells within a simulated microgravity rotating wall bioreactor high aspect ratio vessel system or clinostat system. In the present study, we observed the change of redox status in SH-SY5Y cells after parabolic flight, and studied the effects of key redox molecule, thioredoxin (TRX), during the altered gravity. SH-SY5Y cells were divided into four groups: control cells, control cells transfected with TRX, flight cells and flight cells transfected with TRX. The expression levels of 3-nitrotyrosine (3-NT), inducible nitric oxide synthase (iNOS), TRX and thioredoxin reductase (TRXR) were observed by immunocytochemical method. It was shown that after parabolic flight, the staining of 3-NT and TRX were enhanced, while the expression level of TRXR was down-regulated compared with control. As for flight cells transfected with TRX, the staining of 3-NT and iNOS were weakened compared with flight cells. These results obtained suggest that altered gravity may increase protein nitration, down-regulate TRXR and elicit oxidative stress in SH-SY5Y cells, while TRX transfection could partly protect cells against oxidative stress induced by parabolic flight.
Animals ; Antioxidants ; Cell Line, Tumor ; Humans ; Hypogravity ; Nitric Oxide Synthase Type II ; physiology ; Oxidative Stress ; PC12 Cells ; Rats ; Space Flight ; Thioredoxin-Disulfide Reductase ; physiology ; Thioredoxins ; physiology ; Transfection ; Tyrosine ; analogs & derivatives ; physiology

Helicobacter pylori infection is related to the development of gastric diseases. Our previous studies showed that high thioredoxin-1 (Trx1) expression in H. pylori can promote gastric carcinogenesis. To explore the underlying molecular mechanisms, we performed an isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic analysis of stomach tissues from Mongolian gerbil infected with H. pylori expressing high and low Trx1. Differences in the profiles of the expressed proteins were analyzed by bioinformatics and verified using Western blot analysis. We found three candidate proteins, 14-3-3α/β, glutathione-S-transferase (GST), and heat shock protein 70 (HSP70), in high Trx1 tissues compared with low Trx1 tissues and concluded that cellular stress and redox activity-related proteins were involved in the pathogenesis of gastric cancer associated with H. pylori Trx1.
14-3-3 Proteins/physiology* ; Animals ; Computational Biology ; Gerbillinae ; Glutathione Transferase/physiology* ; HSP70 Heat-Shock Proteins/physiology* ; Helicobacter Infections/complications* ; Helicobacter pylori ; Oxidation-Reduction ; Stomach Neoplasms/etiology* ; Stress, Physiological ; Thioredoxins/physiology*

Reactive oxygen species (ROS) are produced under oxidative stress, such as high oxygen concentration and during the metabolic consumption of oxygen molecules. Male reproductive tissues appear to be continuously exposed to ROS produced by active metabolism. In addition, spermatozoa must pass through a high oxygen environment during the mating process. Thus, to maintain viable reproductive ability, a protective mechanism against oxidative stress is of importance. Here, we overview our current understanding of the cooperative function of antioxidative and redox systems that are involved in male fertility. Superoxide dismutase and glutathione peroxidase are major enzymes that scavenge harmful ROS in male reproductive organs. In turn, glutathione and thioredoxin systems constitute the main redox systems that repair oxidized and damaged molecules and also play a role in regulating a variety of cellular functions. While glutathione functions as an antioxidant by donating electrons to glutathione peroxidase and thioredoxin donates electrons to peroxiredoxin as a counterpart of glutathione peroxidase. In addition, aldo-keto reductases, which detoxify carbonyl compounds produced by oxidative stress, are present at high levels in the epithelia of the genital tract and Sertoli cells of the testis. Since these systems are involved in cross-talk, a comprehensive understanding will be required to maintain the physiological functions of male reproductive system.
Animals ; Antioxidants ; metabolism ; Catalase ; metabolism ; Genitalia, Male ; enzymology ; metabolism ; Glutathione ; biosynthesis ; Glutathione Peroxidase ; metabolism ; Humans ; Male ; Oxidation-Reduction ; Oxidative Stress ; physiology ; Oxidoreductases ; metabolism ; Superoxide Dismutase ; metabolism ; Thioredoxins ; metabolism

BACKGROUNDObstructive sleep apnea (OSA) can cause cognitive dysfunction and may be a reversible cause of cognitive loss in patients with Alzheimer's disease (AD). Chronic exposure to intermittent hypoxia (IH), such as encountered in OSA, is marked by neurodegenerative changes in rat brain. We investigated the change of thioredoxin (Trx), spatial learning and memory in rats exposed to chronic intermittent hypoxia (CIH).

METHODSForty healthy male Sprague-Dawley (SD) rats were randomly divided into four groups of ten each: a CIH+normal saline (CIH+NS group), a N-acetylcystein-treated CIH (CIH+NAC) group, a sham CIH group (sham CIH+NS), and a sham NAC-treated sham CIH (CIH+NAC) group. Spatial learning and memory in each group was assessed with the Morris water maze. Real-time PCR and Western blotting were used to examine mRNA and protein expression of Trx in the hippocampus tissue. The terminal deoxynucleotidyl transferase-mediated dUTP-nick end-labeling (TUNEL) method was used to detect the apoptotic cells of the hippocampus CA1 region.

RESULTSCIH-rats showed impaired spatial learning and memory in the Morris water maze, including longer mean latencies for the target platform, reduced numbers of passes over the previous target platform and a smaller percentage of time spent in the target quadrant. Trx mRNA and protein levels were significantly decreased in the CIH-hippocampus, meanwhile, an elevated apoptotic index revealed apoptosis of hippocampal neurons of rats exposed to CIH. The rats, which acted better in the Morris water maze, showed higher levels of the Trx mRNA and protein in the hippocampus; apoptotic index of the neurons in the hippocampus of each group was negatively correlated with the Trx mRNA and protein levels.

CONCLUSIONThe Trx deficit likely plays an important role in the impaired spatial learning and memory in the rats exposed to CIH and may work through the apoptosis of neurons in the hippocampus.

Animals ; Apoptosis ; Hippocampus ; pathology ; Hypoxia ; complications ; Learning Disorders ; etiology ; Male ; Maze Learning ; Memory Disorders ; etiology ; Rats ; Rats, Sprague-Dawley ; Sleep Apnea, Obstructive ; complications ; Thioredoxins ; physiology

Bone Density ; physiology ; Bone Diseases ; epidemiology ; etiology ; metabolism ; pathology ; Calcium ; metabolism ; China ; epidemiology ; Endemic Diseases ; Fluoride Poisoning ; epidemiology ; etiology ; metabolism ; pathology ; Humans ; Osteoblasts ; physiology ; Oxidative Stress ; Parathyroid Hormone ; metabolism ; Thioredoxins ; metabolism ; Transcription Factor AP-1 ; metabolism

BACKGROUNDThioredoxin is one of the most important redox regulating proteins. Although thioredoxin has been shown to protect cells against different kinds of oxidative stress, the role of thioredoxin in myocardial ischemia and reperfusion injury has not been fully understood. This study was conducted to explore the protective role of human thioredoxin on myocardial ischemia and reperfusion injury and its potential mechanisms.

METHODSPurified human thioredoxin was injected into adult Wistar rats, which were subjected to 30 minutes of myocardial ischemia followed by 2 or 24 hours of reperfusion. We detected 1) the infarct size; 2) the level of malondisldehyde (MDA) in serum; 3) the expression of caspase-9, and cytochrome c in/out of mitochondria by Western blotting; 4) apoptosis by terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) assay and caspase-3 and its protein by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting; 5) the expression of bcl-2 and bax in cardium by immunohistochemical (IHC) assay.

RESULTSHuman thioredoxin reduced myocardial ischemia/reperfusion injury as evidenced by significant decrease of myocardial infarct size (P < 0.01), notable reduction of myocyte apoptosis (P < 0.01), lower systemic oxidative stress level (P < 0.01) after reperfusion for 2 hours, and few inflammatory cell infiltration after reperfusion for 24 hours in rats. Furthermore, treatment with human thioredoxin significantly reduced the release of mitochondrial cytochrome C (P < 0.05), and inhibited the activity of caspase-9 (P < 0.05) and caspase-3 (P < 0.01 in mRNA and P < 0.05 at protein level). Meanwhile, human thioredoxin markedly increased bcl-2 expression (P < 0.05).

CONCLUSIONSThese results strongly suggest that human thioredoxin has cardioprotective effects on myocardial ischemia/reperfusion and its anti-apoptotic role may be mediated by modulating bcl-2 and the mitochondria-dependent apoptotic signaling pathway.

Animals ; Apoptosis ; drug effects ; Caspase 3 ; genetics ; Humans ; Mitochondria, Heart ; drug effects ; physiology ; Mitochondrial Membrane Transport Proteins ; drug effects ; Myocardial Reperfusion Injury ; prevention & control ; Oxidative Stress ; Rats ; Rats, Wistar ; Thioredoxins ; pharmacology

Vitamin D3 up-regulated protein 1 (VDUP1) is a potent growth suppressor that inhibits tumor cell proliferation and cell cycle progression when overexpressed. In a previous study, we showed that VDUP1 knockout (KO) mice exhibited accelerated liver regeneration because such animals could effectively control the expression of cell cycle regulators that drive the G1-to-S phase progression. In the present study, we further investigated the role played by VDUP1 in initial priming of liver regeneration. To accomplish this, VDUP1 KO and wild-type (WT) mice were subjected to 70% partial hepatectomy (PH) and sacrificed at different times after surgery. The hepatic levels of TNF-alpha and IL-6 increased after PH, but there were no significant differences between VDUP1 KO and WT mice. Nuclear factor-kappaB (NF-kappaB), c-Jun-N-terminal kinase (JNK), and signal transducer and activator of transcription 3 (STAT-3) were activated much earlier and to a greater extent in VDUP1 KO mice after PH. A single injection of TNF-alpha or IL-6 caused rapid activation of JNK and STAT-3 expression in both mice, but the responses were stronger and more sustained in VDUP1 KO mice. In conclusion, our findings provide evidence that VDUP1 plays a role in initiation of liver regeneration.
Animals ; Blotting, Western ; Carrier Proteins/*genetics/metabolism ; Cell Proliferation ; *Gene Expression Regulation ; Hepatectomy ; Hepatocytes/*cytology/physiology ; JNK Mitogen-Activated Protein Kinases/genetics/metabolism ; Liver/*physiology ; Male ; Mice, Knockout ; NF-kappa B/genetics/metabolism ; Polymerase Chain Reaction ; *Regeneration ; STAT3 Transcription Factor/genetics/metabolism ; Thioredoxins/*genetics/metabolism