藏灵菇发酵乳对衰老小鼠肝脏线粒体功能的影响

为探究藏灵菇发酵乳对D-半乳糖(D-gal)诱导衰老模型小鼠肝脏线粒体功能的影响,给小鼠皮下注射D-gal,各组连续处理42d后,检测小鼠体重变化、血清丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)活力变化,肝脏线粒体酶活力变化及线粒体通透性变化。结果发现,与对照组相比,D-gal模型组小鼠体重显著降低(P<0.05),ALT及AST分别升高至78.7U/L±10.6U/L(P<0.01)、68.5U/L±12.7U/L(P<0.01),线粒体酶活性显著降低,降低了27.2%(P<0.01),线粒体通透性显著增加,增加了98.4%(P<0.01);与模型组相比,藏灵菇发酵乳保护组小鼠体重显著增加(P<0.05),ALT及AST分别降至54.3U/L±12.4U/L(P<0.01)、47.7U/L±8.9U/L(P<0.01),线粒体酶活性及线粒体通透性均显著恢复(P<0.01)。说明藏灵菇发酵乳可通过抑制线粒体变性改善D-半乳糖(gal)诱导衰老模型小鼠肝损伤。

51例病毒性肝炎的病理与超微病理观察

自1983年3月至1987年9月,我科开展肝活验170余例。其中55例进行了光镜与电镜对比观察,现将资料完整的51例病毒性肝炎的的病理及超微病理观察结果,总结报告如下:材料与方法51例均系本科住院男性青壮年。

Antioxidant dietary approach in treatment of fatty liver: New insights and updates

Non-alcoholic fatty liver disease(NAFLD) is a common clinicopathological condition, encompassing a range of conditions caused by lipid deposition within liver cells. To date, no approved drugs are available for the treatment of NAFLD, despite the fact that it represents a serious and growing clinical problem in the Western world. Identification of the molecular mechanisms leading to NAFLD-related fat accumulation, mitochondrial dysfunction and oxidative balance impairment facilitates the development of specific interventions aimed at preventing the progression of hepatic steatosis. In this review, we focus our attention on the role of dysfunctions in mitochondrial bioenergetics in the pathogenesis of fatty liver. Major data from the literature about the mitochondrial targeting of some antioxidant molecules as a potential treatment for hepatic steatosis are described and critically analysed. There is ample evidence of the positive effects of several classes of antioxidants, such as polyphenols(i.e., resveratrol, quercetin, coumestrol, anthocyanins, epigallocatechin gallate and curcumin), carotenoids(i.e., lycopene, astaxanthin and fucoxanthin) and glucosinolates(i.e., glucoraphanin, sulforaphane, sinigrin and allyl-isothiocyanate), on the reversion of fatty liver. Although the mechanism of action is not yet fully elucidated, in some cases an indirect interaction with mitochondrial metabolism is expected. We believe that such knowledge will eventually translate into the development of novel therapeutic approaches for fatty liver.

Influence of green tea polyphenols on mitochondrial permeability transition pore and Ca^2＋ transport

The authors investigated the influence of green tea polyphenols (GTPs) on the liver mitochondria permeability transition pore (PTP) opening through mitochondria swelling and change of mitochondria membrane potential. The data showed that GTPs had obvious protective effect on the Ca 2+-induced PTP opening in a dose-dependent manner detected by mitochondria swelling. The results were obtained by measuring the change of mitochondria membrane potential through Rh 123. Further experiments were conducted to examine the detailed influence of GTPs on Ca 2+import and export of mitochondria. The results showed that GTPs had remarkably inhibitory effect on the Ca 2+-induced Ca 2+ import in mitochondria; and that they could accelerate Ca 2+-release from mitochondria. Our data provide an alternate interpretation of the potent protective function of GTPs on cell against apoptosis.

Heteroplasmy Level of the Mitochondrial tRNA^(Leu(UUR)) A3243G Mutation in a Chinese Family Is Positively Associated with Earlier Age-of-onset and Increasing Severity of Diabetes

Objective To investigate the mutations of mitochondrial genome in a pedigree with suspected maternally inherited diabetes and deafness and to explore the correlations between the mutations and clinical features. Methods Genomic DNA was isolated from blood leucocytes of each member of the pedigree. The mitochondrial genome was amplified with 24-pair primers that could cover the entire mitochondrial DNA. Direct sequencing of PCR products was used to identify any mitochondrial DNA mutations. Results Family members on the maternal side all harbored the tRNA^Lcu（UUR） A3243G mutation. The paternal side family members did not have the mutation. The age-of-onset of diabetes of the 4 maternal side family members was 15, 41, 44, and 65 years old, and their corresponding heteroplasmy level of the mutation was 34.5%, 14.9%, 14.6%, and 5.9%, respectively. The age-of-onset of diabetes and heteroplasmy level of A3243G mutation were negatively correlated with a correlation coefficient of -0.980（P=0.02）. Meanwhile, patient with high heteroplasmy level of A3243G mutation had relatively low severity of disease. Moreover, 6 reported polymorphisms and 2 new variants were found. Conclusions The main cause of diabetes in this pedigree is the tRNA^Lcu（UUR） A3243G mutation. However, other gene variants may contribute to its pathogenicity. The heteroplasmy level of the tRNA^Lcu（UUR） A3243G mutation is positively associated with earlier age-of-onset and increasing severity of diabetes.

Implications of mitochondrial DNA mutations and mitochondrial dysfunction in tumorigenesis

Alterations in oxidative phosphorylation resulting from mitochondriai dysfunction have long been hypothesized to be involved in tumorigenesis. Mitochondria have recently been shown to play an important role in regulating both programmed cell death and cell proliferation. Furthermore, mitochondrial DNA （mtDNA） mutations have been found in various cancer cells. However, the role of these mtDNA mutations in tumorigenesis remains largely unknown. This review focuses on basic mitochondrial genetics, mtDNA mutations and consequential mitochondrial dysfunction associated with cancer. The potential molecular mechanisms, mediating the pathogenesis from mtDNA mutations and mitochondrial dysfunction to tumorigenesis are also discussed.

Study on mitochondrial DNA diversity among 7 inbred strains of mice

Objective：To study the genetic variation of mitochondrial DNA （mtDNA） among common laboratory strains of inbred mice. Methods： The genetic polymorphism of mtDNA among 4 classical laboratory strains of inbred mice and 3 inbred strains of mice established in China was analyzed by polymerase chain reaction coupled with restriction fragment length polymorphism（PCR-RFLP） and PCR coupled with single-stranded conformation polymorphism（PCR-SSCP）. Results： With regard to the D-loop （Displacement loop, D-loop）, tRNA^ Met＋Glu＋Ile, and ND3 （NADH dehydrogenase subunit 3, ND3） gene fragments of mtDNA from these mice,no variation was revealed by PCR-RFLP at 46 restriction enzyme sites. Further analyzed by PCR-SSCP,the D-loop 5＇fragment and 3＇end fragment of mtDNA from these mice also showed no genetic variation. Conclusion： Owing to maternal mode of inheritance of mtDNA,the results indicate that these common inbred strains of mice share the same maternal lineage.

Exercise and antioxidant supplements in the elderly

Both exercise and aging increase reactive oxygen species （ROS）, which can result in damage to cells. Aging is the result of damage caused by ROS to the mitochondrial genome in post mitotic cells and numerous studies have demonstrated an increase in ROS or their byproducts with exercise. ROS can cause oxidative stress as they overwhelm the antioxidant cellular defenses. Therefore interventions aimed at limiting or inhibiting ROS production, such as supplementation with antioxidant vitamins, should be able to reduce fatigue during muscle contraction and the rate of formation of aging changes with a consequent reduction of the aging rate and disease pathogenesis. However, it has been shown that ROS are essential signaling molecules which are required to promote the health benefits of exercise and longevity. In young individuals, ROS are required for normal force production in skeletal muscle, for the development of training-induced adaptations in endurance performance, as well as for the induction of the endogenous defense systems. Thus, taking antioxidants during training, in young athletes, seems to be detrimental. However, antioxidant supplementation may be expected to be beneficial and is receiving growing attention in the active old population. In this manuscript we review the literature associated with the main areas of interest in this topic.

Effect of moxibustion treatment on cell apoptosis and expressions of heat shock protein and second mitochondrial activator of caspase in acute gastric mucosal lesion of rats

OBJECTIVE:To investigate the effect of moxibustion-acupoint treatment with acupoints of Zusanli(ST 36) and Zhongwan(RN 12) on cell apoptosis and the expressions of heat shock protein(HSP) 60,HSP70 and second mitochondrial activator of caspase(Smac) in rat models of acute gastric mucosal lesion(AGML),and explore the mechanisms underlying protection of gastric mucosal lesion.METHODS:Twenty-four Sprague Dawley rats were divided into 3 groups,blank controlled group(group A),controlled-point group(group B) and acupoint group(group C),8 for each.After 8-day moxibustion treatment in group B and C,gastric lavage of anhydrous ethanol was used to created AGML in all three groups.The Guth method was employed to measure the ulcer index(UI) of gastric mucosal lesion and immunohistochemistry used to measure apoptosis with apoptosis index(AI) and examinetheexpressionsofHSP60,HSP70and Smac.RESULTS:Compared with group A,the expressions of UI,AI,Smac and HSP60 were markedly elevated in group B(P<0.05 or P<0.01).However the expression of HSP70 showed no obvious change(P>0.05);the expressions of UI,HSP60 and HSP70 were markedly elevated in group C(P<0.01) while those of AI and Smac became obviously suppressed(P<0.01).Compared with group B,the expressions of UI,AI and Smac decreased significantly in group C(P< 0.01) while those of HSP60 and HSP70 increased markedly(P<0.01),and the expressions of HSP60 and HSP70 were considerably up-regulated(P< 0.01).CONCLUSION:The moxibustion treatment could alleviate the gastric mucosal lesion caused by anhydrous ethanol,induce the over-expressions of HSP60 and HSP70,and down-regulate the expression of Smac,which could suppress cell apoptosis.

Mitochondrial selfish elements and the evolution of biological novelties

We report the present knowledge about RPHM21, a novel male-specific mitochondrial protein with a putative role in the paternal inheritance of sperm mitochondria in the Manila clam Ruditapes philippinarum, a species with doubly uniparental inheritance of mitochondria （DUI）. We review all the available data on rphm21 transcription and translation, analyze in detail its female counterpart, RPHF22, discuss the homology with RPHM21, the putative function and origin, and analyze their polymorphism. The available evidence is compatible with a viral origin of RPHM21 and supports its activity during spermatogenesis. RPHM21 is progressively accumulated in mitochondria and nuclei of spermatogenic cells, and we hypothesize it can influence mitochondrial inheritance and sex- ual differentiation. We propose a testable model that describes how the acquisition of selfish fea- tures by a mitochondrial lineage might have been responsible for the emergence of DUI, and for the evolution of separate sexes （gonochorism） from hermaphroditism. The appearance of DUI most likely entailed the invasion of at least 1 selfish element, and the extant DUI systems can be seen as resolved conflicts. It was proposed that hermaphroditism was the ancestral condition of bivalves, and a correlation between DUI and gonochorism was documented. We hypothesize that DUI might have driven the shift from hermaphroditism to gonochorism, with androdioecy as transi- tion state. The invasion of sex-ratio distorters and the evolution of suppressors can prompt rapid changes among sex-determination mechanisms, and DUI might have been responsible for one of such changes in some bivalve species. If true, DUI would represent the first animal sex-determination system involving mtDNA-encoded proteins.