To investigate the mechanisms of hepatic injury after biliary obstruction. After a rat model of complete biliary obstruction(CBO) was induced, hepatocyte mitochondria was isolated and the calcium content of mitochondria, the contents of liver malondialdyhyde (MDA) and superoxide dismutase (SOD), the levels of serum T-Bil, ALT, ALP and GGT were measured in each group. Results: After CBO, mitochondrial calcium content, liver MDA and serum T-Bil, ALT, ALP, GGT became increased progressively, compared with control group (Ｐ＜0.05); the liver SOD was decreased markedly (Ｐ＜0.05). Mitochondrial calcium content was highly positively correlated with liver MDA content, serum ALT and ALP, r values were 0.967, 0.924 and 0.919 respectively (Ｐ＜0.01). The liver MDA content was highly positively correlated with serum ALT and ALP, r values were 0.949 and 0.843 respectively (Ｐ＜0.01). Conclusions: Mitochondrial calcium overload and liver lipid peroxidation may be the important mechanisms of hepatic injury induced by biliary obstruction.
Purpose To investigate the relationship between mitochondrial DNA 11778 mutation and clinical characteristics of patients with Laber is hereditary optic neuropathy(LHON). Methods PCR RFLPs (MaeⅢ) and mutation specific primer PCR(MSP-PCR) were used simultaneously to detect mitochondrial DNA 11778 mutation. Results Among 10 subjects who habored 11778 mutation,one was a carrier and nine were patients with LHON.Of the nine patients,six were males and three were females.The age of onset ranged from 12 to 25 years old and the onset interval of the two eyed varied between 0 to 6 months. The visual acuity was CF/10cm-0.1 except one who lost her vision after delivery but recovered gradually.The results of visual field,VEP and color vision were abnormal but ERG and systemic status were all normal. Conclusion Molecular biological detection of the ten subjects showed that they all habored mtDNA 11778 mutation.The existence of carrier and visual recovery imlied that mtDNA mutation was a primary cause of LHON,but other factors such as endocrine disorder might influence the pathogenesis of LHON. (Chin J Ocul Fundus Dis,1998,14:156-158)
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.
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 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.
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 observe the retinal manifestations and classification of mitochondrial encephalomyopathy，and explore the relationship between retinopathy and systemic manifestations.Method The clinical data of 88 inpatients with mitochondrial encephalomyopathy were retrospectively analyzed，in whom 12 patients（24 eyes）with retinal manifestations who diagnosed by ophthalmology consultation and complete medical records were collected. There were nine males and three females aged from 14 to 33 years with the mean age of（20.1±7.0）years. The disease duration ranged from 2.5 to 20 years，with the mean of（9.5±6.8）years. All the patients had the eye symptoms of the different degree，such as limbs weakness，hearing decline and central nervous system symptoms. Ophthalmologic examination including best corrected visual acuity，slit lampa microscope，indirect ophthalmoscopy，noncontact Tonometer，ptosis，ocular movement，pupillary reflex and color fundus photography. Among the patients，three，one，two and five patients had undergone fundus fluorescein angiography（FFA），optical coherence tomography（OCT），lectroretinogram（ERG）and visual field examination respectively. Diabetic retinopathy were divided into “salt and pepper”， retinitis pigmentosa（RP），retinal pigment epithelium（RPE），choroidal capillary atrophy and simplex optic atrophy according to the inspection results.Results All the patients′ both eyes were involved，the disease degree of bilateral eyes was accordant. The ptosis and（or）eye movement limitation were found in nine patients（75.0%），and decreased visual acuity was in six patients（50.0%）.“Salt and pepper” was found in six patients（12 eyes），presenting retinal granular pigmentation and depigmentation；the visual acuity was 0.4-1.2；no central nervous system symptoms were found in patients，such as hearing decline，twitch，ataxia and hypophrenia. RP was found in one patient（two eyes），presenting retinal cells sample pigmentation，retinal vessel shrink，optic atrophy；the vision were light perception in both eyes；hypophrenia，hearing decline，bilateral lower limbs pain and onset twitch were also found in them. RPE and choroidal capillary atrophy were found in three patients（six eyes），the choroidal great vessels and flake pigment accumulation surrounding the retina were observed；the visual acuity was hand movement0.7；limbs weakness was found in two patients；hearing decline was found in three patients；barylalia and hypophrenia were found in two patients；somnolence was found in one patient. Simplex optic atrophy was found in two patients（four eyes）；the vision was 0.1-0.7；central nervous system symptoms were found in patients，such as limbs weakness，twitch，hypophrenia and headache.Conclusion Retinopathy types is concerned with visual prognosis and central nervous system symptoms.
Objective To investigate the preventive and therapeutic effects and the mechanisms of pyrrol idine dithiocarbamate (PDTC) on the atrophy of denervated skeletal muscle. Methods Thirty adult Wistar rats of either gender, weighing (200 ± 10) g were randomly divided into 3 groups: group A (n=6, control group), group B (n=12, denervation group), and group C (n=12, PDTC treatment group). The sciatic nerves of the rats were only exposed without cutting off in group A, and the rats were made denervated gastrocnemius models in groups B and C. PDTC of 100 mg/(kg•d) was injected peritoneally in group C and an intraperitoneal injection of the same amount normal sal ine was given in group B. After 14 and 28 days, the gastrocnemius was harvested to measure the ratio of muscle wet weight; the levels of nuclear factor of κB (NF-κB)p65 protein and the opening of the mitochondrial permeabil ity transition pore (MPTP) in the gastrocnemius were detectedrespectively by Western blot and laser confocal scanning microscope; and the apoptotic cells in atrophic muscle were measured with TUNEL. Results The ratio of muscle wet weight in group A was 1.039 ± 0.115, and it significantly decreased in groups B and C (P lt; 0.05); after 14 and 28 days of operation, the ratio of muscle wet weight in group C significantly increased when compared with those in group B (P lt; 0.05). The expression of NF-κB p65 protein in group A was 0.224 ± 0.041; the expressions of NF-κB p65 in groups B and C significantly increased when compared with that in group A (P lt; 0.05); however, the expression of NF-κB p65 in group C was significantly lower than that in group B (P lt; 0.05). The MPTP fluorescence intensity in group A was 31.582 ± 1.754; the MPTP fluorescence intensity was significantly lower in groups B and C than in group A (P lt; 0.05), and the MPTP fluorescence intensity in group C was significantly higher than that in group B (P lt; 0.05). The rate of apoptosis in group A was 4.542% ± 0.722%; after 14 and 28 days of operation, the rates of apoptosis significantly increased when compared groups B and C with group A, and signiticantly decreased when compared group C with group B (P lt; 0.05). Conclusion PDTC can retard denervated skeletal muscle atrophy, and the effect may have a relationship with its inhibition on NF-κB, the opening of the MPTP, and the ratio of apoptosis.
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.
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.