Mitochondrial quality control includes mechanisms such as mitochondria-derived vesicles, fusion / fission and autophagy. These processes rely on the collaboration of a variety of key proteins in the inner and outer membranes of mitochondria to jointly regulate the morphological structure and functional integrity of mitochondria, repair mitochondrial damage, and maintain the homeostasis of their internal environment. The imbalance of mitochondrial quality control is associated with leukemia. Therefore, by exploring the mechanisms related to mitochondrial quality control of various leukemia cells and their interactions with immune cells and immune microenvironment, this article sought possible targets in the treatment of leukemia, providing new ideas for the immunotherapy of leukemia.
Objective To investigate the effect of S-adenosylmethionine (SAM) on mitochondrial injury that was induced by ischemia-reperfusion in rat liver. Methods Fifty-four rats were randomly divided equally into 3 groups: control group, ischemia-reperfusion group (I/R group), and SAM-treated group (SAM group). Hepatic ischemia had been only lasted for 30 min by obstructing the blood stream of hepatic portal vena (the portal vena was only separated but not obstructed in control group). The rats of SAM group received SAM intraperitoneally 2 h prior to ischemia. Blood samples of each group were collected from the inferior cava vena at 0, 1 and 6 h after reperfusion and the serum levels of AST and ALT were detected. Mitochondrial super oxidedismutase (SOD), malondialdehyde (MDA), adenosine triphosphate (ATP) and energy charge (EC) in samples of liver tissue were detected, and the mitochondrial ultrastructure was observed with electronmicroscope. Results The serum levels of AST, ALT and mitochondrial MDA at 0, 1 and 6 h after reperfusion in the I/R group were significantly higher than those in the control group, whereas the levels of mitochondrial SOD, ATP and EC were significantly lower than those in the control group (P＜0.01). Except the value of 0 h, when it comes to SAM group, the levels of AST, ALT and mitochondrial MDA were significantly lower (P＜0.05) and the levels of mitochondrial SOD, ATP and EC were significantly higher (P＜0.05, P＜0.01) than those in the I/R group, respectively. The mitochondrial ultrastructure was injured obviously in I/R group when compared with that in control group. The number of mitochondria decreased and the mitochondria swelled, making the crista became obscure and the density of matrix became lower. The above changes in SAM group were less obvious when compared with those in I/R group. Conclusion SAM may protect mitochondrion against hepatic ischemia injury, since it may prevent mitochondrial lipid peroxidation, increase ATP, and eventually improve energy metabolism after ischemia-reperfusion.
ObjectiveTo investigate the expression of mitochondrial transcription factor A (TFAM) in colon cancer and the effect of its expression on proliferation of colon cancer cell. MethodsThirty cases of colon cancer in the First Affiliated Hospital of Sun Yat-sen University from March 2013 to April 2013 were studied. TFAM mRNA was detected both in colon cancer tissue and para-cancer tissue by real-time PCR. TFAM mRNA and protein were detected in normal colon cell strain and colon cancer strains SW480, HT-29, and HCT116 by real-time PCR and Western blot, respectively. The proliferation of SW480 cells was evaluated after up-regulating TFAM. ResultsThe expression of TFAM mRNA in the colon cancer tissue was significantly higher than that in the para-cancer tissue (P < 0.000 1). The expressions of TFAM mRNA were obviously increased in the SW480, HT-29, and HCT116 cells as compared with the normal colon cell strain (P value was 0.000 8, 0.002 3, and 0.000 6, respectively), among which the most notable increase was detected in the SW480 cells. The expressions of TFAM protein were obviously increased in the SW480, HT-29, and HCT116 cells as compared with the normal colon cell strain (P value was 0.000 2, 0.003 8, and 0.001 6, respectively), among which the most notable increase was detected in the SW480 cells. After up-regulating TFAM by plasmid transfection, the proliferation of the pcDNA3.1-TFAM-SW480 cell was increased significantly as compared with the pcDNA3.1-SW480 cell at 96 h and 120 h after transfection by the MTT test (P < 0.000 1). The proliferation of the pcDNA3.1-TFAM-SW480 cell was increased significantly as compared with the pcDNA3.1-SW480 cell at 48 h after transfection by the BrdU test (P < 0.001 0). ConclusionTFAM expression is high in colon cancer. Up-regulated TFAM could promote the proliferation of colon cancer cells.
Objective To investigate the protective effects of ischemic postconditioning (IPo) on ischemiareperfusion (I/R) myocardium and the relationship with mitochondrial adenosine triphosphate (ATP) sensitive K+ channels (mitoKATP) and provide evidences to the development of druginduced postconditioning. Methods Langendorff models were established in 40 Wistar rats which were divided into 5 groups by random number table with 8 rats in each group. Normal control group(NC group): the rat hearts were continuously reperfused by KrebsHenseleit bicarbonate buffer (K-HB) for 100 min without any other treatment; I/R group: the rat hearts underwent a 40-min global ischemia followed by a 60-min reperfusion; IPo group: after a 40-min global ischemia, the process of 10-second reperfusion followed by a 10-second ischemia was repeated 6 times, then there was a continuous 58min reperfusion; 5-hydroxydecanoic acid(5-HD) group: after a 40min global ischemia, hearts with 5HD(100 μmol/L) K-HB were reperfused for 15min and then perfused without 5HD for 45min；IPo+5-HD group: after a 40-min global ischemia, the process that the isolated hearts with 5-HD(100 μmol/L) KHB were reperfused for 10second followed by a 10second ischemia was repeated 6 times, then the hearts with 5-HD(100 μmol/L) KHB were continuously [CM(159mm]perfused for 13-min followed by reperfusion without 5-HD(100 μmol/L) K-HB for 45-min. The cardiac function,coronary flow(CF), cardiac troponin I(cTnI) content in coronary effluent, the area of acute myocardial infarction (AMI) and myocardial ultrastructure were observed. Results Left ventricular developed pressure(74.3±3.3 mm Hg vs. 57.1±3.3 mm Hg,t=1300, P=0.000),+dp/dtmax(1 706.6±135.6 mm Hg/s vs. 1 313.3±96.2 mm Hg/s,t=6.28,P=0.000),－dp/dtmax(1 132.8±112.1 mm Hg/s vs. 575.7±67.7 mm Hg/s,t=13.48, P=0.000) and CF(6.49±0.30 ml/min vs. 3.70±0.24 ml/min,t=28.6,P=0.000) in IPo group were higher than those in I/R group. Left ventricular enddiastolic pressure(10.9±1.7mm Hg vs. 26.2±1.5 mm Hg,t=－19.21, P=0000)and cTnI content in coronary effluent (0.62±0.01 ng/ml vs. 0.71±0.01 ng/ml, t=-12.00,P=0.000) were lower than those in I/R group; the area of AMI decreased 20.8％ compared with that in I/R group (Plt;0.05). The myocardial protective effect in IPo+5HD group was similar with that in IPo group, but lower than that in IPo group. The electron microscope showed that IPo and IPo+5HD could reduce myocardial fiber damage and mitochondrial damage caused by I/R. Conclusion IPo can protect I/R myocardium, which is achieved mainly by activating mitoK-ATP channels.
Nuclear factor-erythroid 2-related factor 2 (Nrf2) is an important factor for cells to resist oxidative stress and electrophilic attack. It is involved in the formation and control of oxidative stress defense pathways. It is associated with oxidative stress-related diseases, including cancer, neurodegenerative diseases, cardiovascular diseases and aging, and is a potential pharmacological target for the treatment of chronic diseases. This article will review the important role of Nrf2 in the regulation of cell proliferation, including direct regulation of cell proliferation, regulation of reactive oxygen species, intracellular metabolism, regulation of mitochondrial function, cell lifespan and inflammatory response. The aim is to provide a theoretical basis for further research on how to use Nrf2 to regulate cell proliferation.
Objective To explore the relationship between microsatellite instability （MSI） and gastric cancer. Methods The related literatures at home and abroad were consulted and reviewed. Results The MSI is the replication errors caused by mismatch repair system defects. Gastric cancer which exhibiting MSI has characteris clinicopathological feature and prognosis. Detection the MSI of precancerous lesions and gastric cancer tissues can evaluate the risk and prognosis of gastric cancer. MSI include nuclear microsatellite stability （nMSI） and mitochondrial microsatellite instability （mtMSI）. Conclusions MSI plays an important role in the occurrence and development of gastric cancer. MSI may become a important indicator to forecast precancerosis risks and clinical prognosis of gastric cancer.
Objective To investigate the role of mitochondrial adenosine triphosphatesensitive potassium channel(mitoKATP) in immature myocardial ischemic preconditioning, and to provide evidence for immature myocardial protection. Methods Langendorff isolated heart infused model was used in the experiment. Twentyfour rabbits (aged from 14 to 21 days) were randomly divided into 4 groups：ischemiareperfusion group（I/R group）, myocardial ischemic preconditioning group(E1 group), 5hydroxydecanoate(5-HD) group (E2 group) and Diazoxide (Diaz) group(E3 group). Hemodynamics recovery rate, myocardial water content(MWC), the leakage rates of serum creatine kinase and lactate dehydrogenase, adenosine triphosphate content, superoxide dismutase activity, malondialdehyde content, myocardial cell Ca2+ content and myocardial mitochondrial Ca2+ content, myocardial mitochondrial Ca2+-ATPase activity, the adenosine triphosphate(ATP) synthesizing ability of myocardial mitochondria were tested, and myocardial ultrastructure was observed via electron microscopy. Results The hemodynamics recovery rate, myocardial water content(P＜0.05), adenosine triphosphate content, superoxide dismutase activity, myocardial mitochondrial Ca2+-adenosine triphosphyatase(ATPase) activity and the ATP synthesizing ability of myocardial mitochondria of the rabbits in E1 and E3 group were significantly better than that in I/R group and E2 group(P＜0.05). Malondialdehyde content, the leakage rates of serum creatine kinase and lactate dehydrogenase, myocardial cell Ca2+ content and myocardial mitochondrial Ca2+ content of the rabbits in E1 group and E3 group were significantly lower than that in I/R group and E2 group (P＜0.05). The myocardial ultrastructure injury in E1 and E3 group were significantly reduced compared with that in I/R and E2 group. Conclusion Myocardial ischemic preconditioning has significant protective effects on immature myocardium. Its mechanism may be related to the activation of mitoKATP.
The main function of mitochondrial fusion protein 1 （Mfn1） and mitochondrial fusion protein 2 （Mfn2） was originally thought to be just regulating the fusion of mitochondrial outer membrane. But in recent years，many studies on these two proteins show that they are involved in many important cellular physiological processes including proliferation，apoptosis，necrosis and regulation of respiratory function and oxidative metabolism. There are many aspects of the influenceof Mfn1 and Mfn2 on cardiomyocyte，which have not been thoroughly studied yet，sometimes with even contradictoryconclusions. But these two proteins definitely have significant impact on the growth，development and physiological functionof cardiomyocyte. To investigate the function and mechanism of Mfn1 and Mfn2 in various physiological processes of cardiomyocyte is of great significance for in vitro studies of physiological functions of cardiomyocyte and technological development of myocardial tissue engineering and transplantation in vivo. This article mainly focuses on recent research progress of the influence of Mfn1 and Mfn2 on various physiological functions of cardiomyocyte.
Objective To explore the feasibility of identifying clonal origin of hepatocellular carcinoma (HCC) by analyzing the mitochondrial DNA D-Loop region variations. Methods Forty-two patients with a total of 112 HCC nodules consequentially hospitalized for radical resection of HCC in the department of hepatobiliary surgery of the First Affiliated Hospital of Guangxi Medical University from April 2004 to August 2007 were included for study group (multinodular HCCs). Control group included 20 cases of HCC (40 samples) hospitalized in the same period that consisted of two sub-groups: control groupⅠconsisted of 16 cases of single nodular HCC that each had two pieces of inconsecutive tumor tissues and control groupⅡconsisted of 4 cases of HCC with portal vein tumor embolus whose tumor tissues and portal vein tumor embolus were collected simultaneously. Normal control included 5 patients who were donors for liver transplantation or underwent liver trauma without any liver disease. Polymerase chain reaction (PCR) and direct sequencing were applied to study the mtDNA D-Loop region. The sequences of multinodular lesions were compared among different groups. Results For all the 42 cases of the study group, basic group variations appeared in 131 sites (131/1 122, 11.7%, the number 1 122 was the length of mtDNA D-Loop) with point mutation in 15 sites, insert in 9 sites, and deletion in 16 sites. And of all the variations in the study group, 98 were polymorphism. In study group, 20 cases were categorized as multicentric occurrence (MO) based on their variant mtDNA D-Loop sequences in each nodule from the same patient. And 22 cases were characterized as intrahepatic metastasis (IM) based on the identical mtDNA D-Loop sequences found in each nodule from the same patient. In all 20 cases in the control group, the inconsecutive tumor tissues or the portal vein tumor embolus and original tumors shared identical mtDNA D-Loop sequences. For the normal control group, basic group variations appeared in 14 sites, and they were all polymorphism including a new polymorphism (NT 479 Agt;G). Conclusions There is a high rate of changes in mtDNA D-Loop region. And our study speculates a novel discrimination of MO and IM origins among multinodular HCCs using PCR and direct sequencing of the mtDNA D-Loop sequences.
Objective To review the research progress of mitochondrial dynamics mediated by optic atrophy 1 (OPA1) in skeletal system diseases. MethodsThe literatures about OPA1-mediated mitochondrial dynamics in recent years were reviewed, and the bioactive ingredients and drugs for the treatment of skeletal system diseases were summarized, which provided a new idea for the treatment of osteoarthritis. Results OPA1 is a key factor involved in mitochondrial dynamics and energetics and in maintaining the stability of the mitochondrial genome. Accumulating evidence indicates that OPA1-mediated mitochondrial dynamics plays an important role in the regulation of skeletal system diseases such as osteoarthritis, osteoporosis, and osteosarcoma. Conclusion OPA1-mediated mitochondrial dynamics provides an important theoretical basis for the prevention and treatment of skeletal system diseases.