Mitochondrial DNA haplogroup associated with sperm motility in the Han population

In this study, we aimed to determine whether the main mitochondrial DNA （mtDNA） haplogroups of the Han people have an impact on spermatozoa motility, We recruited 312 men who were consecutively admitted to two affiliated hospitals of College of Medicine, Zhejiang University from May 2011 to April 2012 as part of fertility investigations. Semen and whole blood samples were collected from the men. We determined the mtDNA haplogroups by analysing the sequences of mtDNA hypervariable segment I and testing diagnostic polymorphisms in the mtDNA coding region with DNA probes, No significant differences were found in the clinical characteristics of the mtDNA haplogroup R and non-R （P〉0.05）. Our results suggest that mtDNA haplogroup R is a strong independent predictor of sperm motility in the Han population, conferring a 2.97-fold （95% confidence interval： 1.74-4.48, P〈0.001） decreased chance of asthenozoospermia compared with those without haplogroup R.     

线粒体核糖体蛋白与人类线粒体疾病

哺乳动物线粒体核糖体(mitochondrial ribosome,mitoribosome)在漫长的进化阶段经过一系列的结构重组,rRNA比例降低,新增了部分线粒体核糖体蛋白(mitochondrial ribosomal proteins,MRPs),成为蛋白含量最丰富的核糖体.所有MRPs均为核基因编码,在细胞质中合成,再转运到线粒体,与线粒体基因(mitochondrial DNA,mtDNA)编码的两种rRNA结合.mtDNA除编码tRNA和rRNA外,还编码组成线粒体呼吸链复合体的13种蛋白质.由于线粒体核糖体负责翻译这13种蛋白,MRPs和其他翻译工具的突变和缺陷可造成线粒体的相关疾病.     

Tanshinone IIA protects rat primary hepatocytes against carbon tetrachloride toxicity via inhibiting mitochondria permeability transition

Tanshinone IIA (Tan IIA), one of the key components of Salvia milthorrhiza Bunge (Lamiaceae), is used to treat liver disease. The present study was carried out to investigate the possible mechanisms involved in the hepatoprotective effects of Tan IIA on carbon tetrachloride (CCl₄)-induced hepatocyte toxicity. In cultures treated with 1 or 2 μM CCl₄, Tan IIA (10–75 μM) significantly increased hepatocyte survival rates. However, only at a concentration of 75 μM could Tan IIA partially reverse the CCl₄ (3 μM)-induced decrease of survival rate (34?±?3% vs. 18?±?3%, n?=?8, p?<?0.01). In isolated mitochondria energized with succinate, Tan IIA could inhibit the large swelling effect induced by CCl₄ (1 and 2 μM). Base on these results, Tan IIA could protect rat primary cultured hepatocytes from CCl₄-induced toxicity partially by the inhibitory effect on the opening of mitochondrial permeability transition (MPT).     

Seizures,antiepileptics, antioxidants and oxidative stress: an insight for researchers

Background: Neuronal hyperexcitability and excessive production of free radicals have been implicated in the pathogenesis of a considerable range of neurological disorders, including epilepsy. The high rate of oxidative metabolism, coupled with the low antioxidant defenses and the richness in polyunsaturated fatty acids, makes the brain highly vulnerable to free radical damage. The increased susceptibility of the brain to oxidative damage highlights the importance of understanding the role of oxidative stress in the pathophysiology of seizures. Objectives: The present review aims not only to address the link between mitochondrial dysfunction, oxidative stress and seizures, but also the modulation of the pro-oxidant/antioxidant balance following seizures and treatment with antioxidants and antiepileptic drugs. Methods: A literature review revealed that there are articles that address the role of oxidative stress and mitochondrial dysfunction in neurological disorders, including those involving different seizure models where the modulation of the pro-oxidant/antioxidant balance by seizures per se and by antioxidant agents is discussed. However, the critical role of oxidative stress in all seizure models is not uniform. Therefore, there is a need for a review article that will address all these issues together. Results/conclusions: The experimental and clinical data suggest a putative role of oxidative stress in the pathophysiology of certain seizure types. The pro-oxidant/antioxidant balance is not only modulated by seizures per se, but also by antiepileptic drugs. The ability of antioxidants for reducing the seizure manifestations and the accompanying biochemical changes (i.e., markers of oxidative stress) further supports a role of free radicals in seizures and highlights a possible role of antioxidants as adjuncts to antiepileptic drugs for better seizure control.     

mtDNA variation in the Buryat population of the Barguzin Valley: New insights into the micro-evolutionary history of the Baikal area

Abstract

Background: Southern Siberian populations, including the Buryat, have been of great interest in investigating the exchanges between Eastern and Western Eurasia and understanding the peopling of Siberia and the New World.

Aim: Previous studies mainly employed a phylogenetic approach, and thus used pooled samples to detect a maximum of variability. As different sampling strategies may result in different pictures of a population's evolutionary history, we proposed in this study to focus on a local Buryat population selected on the basis of geographical, archaeological and ethno-historical data.

Subjects and methods: This study investigated a local population from the Barguzin Valley, on the north-western shores of Lake Baikal identified as the most likely place of Buryat origin. We analysed mitochondrial DNA (mtDNA) RFLPs markers, HVS-I and HVS-II sequences to discuss the genetic variability of this population, and to compare our local sample with pooled Buryat samples and neighbouring Siberian populations.

Results: The Barguzin Buryat sample shows depressed neutrality scores compared to the pooled Buryat sample, and different genetic affinities with the Mongol and Turco-Evenk populations.

Conclusion: These results underline the need to use local samples, in addition to pooled samples, to investigate the history of human populations at the micro-evolutionary level.     

Protective effect of curcumin against arsenic-induced apoptosis in murine splenocytes in vitro

Arsenic is a potent environmental pollutant and immunotoxic agent. Curcumin is a natural anti-oxidant used to treat a broad variety of diseases. Here, the effects were investigated of curcumin on sodium arsenite-induced apoptosis in murine splenocytes in vitro. Cells were exposed to sodium arsenite (NaAsO₂, 5 µM) with and without curcumin (5 and 10 µg/ml) and incubated at 37°C for 12?h. NaAsO₂ caused a decrease in cell viability and induction of apoptosis. These outcomes were concurrent with increases in the numbers of cells with reactive oxygen species generation, loss of mitochondrial transmembrane potential, an increase in the frequency of cells with sub-G₁ DNA content, and DNA fragmentation. Co-administration of curcumin with the NaAsO₂ caused significant recoveries in cell viability values and mitigation of the induced apoptosis-related molecular changes. A significant protection against apoptosis parameters in murine splenocytes simultaneously treated with NaAsO₂ and curcumin suggested a protective efficacy of curcumin. From the results it is concluded that the immuno-modulation exerted by curcumin might be attributed to its multifaceted effects including its anti-oxidative and anti-apoptotic properties. These findings have implications not only for the under-standing of the toxicity of arsenic to murine splenocytes in vitro but are also potentially important for developing preventive and/or corrective strategies against/during chronic arsenicosis.     

Dexamethasone-induced apoptosis in PC12 cells

Abstract

This study aims to evaluate the cytotoxicity and damage of dexamethasone (DEX) on rat pheochromocytoma (PC12) cells by determining cell viability, Hoechst 33342 staining, mitochondrial depolarization assays, opened mitochondrial permeability transition pores (MPTPs) detection, and measurement of Caspase-3 and Bcl-2 activities. The results show that DEX inhibits PC12 cell growth and decreases their viability in a remarkable dose-dependent manner. Our results also reveal that DEX exposure causes morphologic changes, opening of MPTPs and mitochondrial depolarization, upregulates Caspase-3 expression, and suppresses Bcl-2 expression in PC12 cells. These results suggest that DEX-induced apoptosis may be mediated through mitochondrial dysfunction.     

The role of dynamin-related protein 1 in cancer growth: a promising therapeutic target?

Mitochondrial functions are altered in many human diseases including cancer. Development of mitochondria-targeted therapies, either through restoring normal mitochondrial function or promoting mitochondrial-induced cell death, is one of the attractive strategies to improve the outcome of cancer treatment. Recent advances have revealed the important functional involvement of mitochondrial dynamics in cancer biology. Dynamin-related protein 1 (Drp1), a member of the dynamin family of GTPases required for mitochondrial fission, has been found upregulated in certain types of cancers, such as lung and breast cancers. In addition, the roles of Drp1 in cell cycle progression, genome instability, cell migration and apoptosis in cancer cells have also been recently uncovered. These findings raise the possibility of targeting Drp1-mediated mitochondrial fission as an effective therapy for treating cancer. This article explores the function of Drp1 in cancer cells and discusses the theoretical basis for the development of potential targeted therapy.     

MOMP in the absence of BH3-only proteins

The minimum requirement for mitochondrial apoptosis has been controversial ever since the discovery of BCL-2 as a cell death regulator. In this issue of Genes & Development, O''Neill and colleagues (pp. 973–988) end a long-standing debate by creating a cellular system free of BCL-2 family proteins, thereby identifying the outer mitochondrial membrane rather than BH3-only proteins as the only requirement for BAX/BAK activation and mitochondrial outer membrane permeabilization (MOMP).