OBJECTIVETo study the role of Ca2+ overload and energy metabolism in mitochondria in masticatory muscle dysfunctional induced by occlusal trauma.

METHODSMitochondrial Ca2+ contents were measured with atomic emission spectrophotometer. Mitochondrial ATP and ADP contents were measured with high performance liquid chromatography.

RESULTS(1) Mitochondrial Ca2+ contents of masseter muscle ipsilateral to metal splint in ten and twenty days' experimental groups and that contralateral to metal splint in twenty days' experimental group increased significantly (P < 0.05). (2) Mitochondrial ATP contents of masseter muscle ipsilateral to metal splint in experimental groups were higher than that in control groups and contralateral to metal splint after twenty days. (3) Mitochondrial Ca2+ contents of masseter muscle ipsilateral to metal splint were significantly negatively correlated to the mitochondrial ATP contents (r = -0.780, P < 0.05).

CONCLUSIONCa2+ overload in mitochondria depresses ATP production, which results in energy metabolism disorder in masticatory muscle cells. It may play an important role in the mechanism that occlusal trauma results in masticatory muscle dysfunction.

Adenosine Diphosphate ; chemistry ; Adenosine Triphosphate ; chemistry ; Animals ; Calcium ; chemistry ; Energy Metabolism ; Masseter Muscle ; chemistry ; injuries ; Mitochondria, Muscle ; chemistry ; Rabbits

The morbidity of neurodegenerative diseases are increased in recent years, however, the treatment is limited. Poly ADP-ribosylation (PARylation) is a post-translational modification of protein that catalyzed by poly(ADP-ribose) polymerase (PARP). Studies have shown that PARylation is involved in many neurodegenerative diseases such as stroke, Parkinson's diseases, Alzheimer's disease, amyotrophic lateral sclerosis and so on, by affecting intracellular translocation of protein molecules, protein aggregation, protein activity, and cell death. PARP inhibitors have showed neuroprotective efficacy for neurodegenerative diseases in pre-clinical studies and phase Ⅰ clinical trials. To find new PARP inhibitors with more specific effects and specific pharmacokinetic characteristics will be the new direction for the treatment of neurodegenerative diseases. This paper reviews the recent progress on PARylation in neurodegenerative diseases.
ADP-Ribosylation ; Humans ; Neurodegenerative Diseases ; physiopathology ; Poly Adenosine Diphosphate Ribose ; Poly(ADP-ribose) Polymerases ; metabolism

To compare the cardiotoxicity induced by ropivacaine and bupivacaine and to investigate the mechanism of cardiotoxicity, 24 mature New Zealand rabbits were divided randomly into control group (group C), ropivacaine group (group R) and bupivacaine group (group B). Hearts were drawn out rapidly from the anesthetized animals and cardiac perfusion was performed immediately. Ropivacaine 500 ng/ml (group R) or bupivacaine 500 ng/ml (group B) was added to the perfusion solution. Ventricular myocardial ATP, ADP and AMP were measured with high performance liquid chromatogram. The ability of myocardial mitochondria oxidation to pyruvate or palmitoylcarnitine was detected with Clark electrode. Our results showed that myocardial ATP and ADP decreased significantly (P < 0.05) in group R and most significantly (P < 0.01) in group B as compared with group C. Myocardial ATP and ADP decreased most significantly (P < 0.01) in group B as compared with group R. The changes of myocardial AMP revealed significant difference among three groups. The changes of pyruvate oxidation exhibited no significant difference among the three groups. Palmitoylcarnitine oxidation decreased markedly (P < 0.05) in group R and most significantly (P < 0.01) in group B as compared with group C. The present study indicated that the inhibition of lipid substrate oxidation may be responsible for the cardiotoxicity induced by bupivacaine and ropivacaine. The cardiotoxicity induced by ropivacaine is far more less than bupivacaine.
Adenosine Diphosphate ; metabolism ; Adenosine Triphosphate ; metabolism ; Amides ; toxicity ; Anesthetics, Local ; toxicity ; Animals ; Bupivacaine ; toxicity ; Energy Metabolism ; In Vitro Techniques ; Mitochondria, Heart ; metabolism ; Myocardium ; metabolism ; Oxidation-Reduction ; Rabbits ; Random Allocation

OBJECTIVE: The content changes of energy substances in the cardiac muscle of rat killed by different manners were investigated to elucidate evidence that can be used to determine the modes of death and postmortem interval. METHODS: One hundred and eighty rats were randomly allocated into 3 groups and killed by bleeding, suffocating, and neck breaking, respectively. The contents of ATP, ADP, and AMP in the cardiac muscle of rats killed by the different manners at different death intervals (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, and 24 h) were measured by HPLC. RESULTS: There were significant differences observed in the contents of ATP and AMP in the rats' cardiac muscle in different groups at most of the intervals (P < 0.05) and at all of the intervals within the same group (P < 0.01), but no differences were found in the ADP contents in any of the group at most of the intervals. CONCLUSION The content changes of energy substances (ATP and AMP) in the cardiac muscle of dead rats may provide a basis for determination of the death manners and postmortem intervals.
Adenosine Diphosphate/metabolism* ; Adenosine Monophosphate/metabolism* ; Adenosine Triphosphate/metabolism* ; Animals ; Asphyxia/metabolism* ; Cause of Death ; Cervical Vertebrae/injuries* ; Chromatography, High Pressure Liquid ; Female ; Male ; Myocardium/pathology* ; Postmortem Changes ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Shock, Hemorrhagic/metabolism* ; Time Factors

BACKGROUND: ADP-ribosyl pyrophosphatases (ADPRase) has been known to catalyze the hydrolysis of ADP-ribose to ribose-5-phosphate and AMP. The role of ADPRase has been suggested to sanitize the cell by removing potentially toxic ADP-ribose. In this study, we examined the effect of nitric oxide on ADPRase activity in macrophages. METHODS: ADPRase activity was measured in NO-inducing J774 cells. For in vitro experiments, recombinant human ADPRase was prepared in bacteria. RESULTS: ADPRase activity was increased by the treatment of exogenous NO generating reagent, sodium nitroprusside (SNP), in J774 cells. The increased ADPRase activity was mediated by the post-translational modification, likely to cause cADP-ribosylation via nitrosylation of cysteine residue on the enzyme. The stimulation with endogeneous NO inducers, TNF-alpha/IFN-gamma, also increased ADPRase activity through NO synthesis. Futhermore, ADPRase activity may be mediated by the post-translational modification of ADPRase, ADP-ribosylation. CONCLUSION: These results indicate that NO synthesized by macrophage activation plays a critical role in the increase in ADPRase activity following ADP-ribose metabolism.
Adenosine Diphosphate Ribose* ; Bacteria ; Cysteine ; Humans ; Hydrolysis ; Macrophage Activation ; Macrophages ; Metabolism ; Nitric Oxide* ; Nitroprusside ; Protein Processing, Post-Translational ; Pyrophosphatases

Transient receptor potential (TRP) superfamily is a superfamily of cation channels that can be divided into seven subfamilies. TRPM2 is the second member of the TRPM subfamily, which includes eight members, namely TRPM1-8. TRPM2 is widely expressed in excitable and non-excitable cells, where it forms a Ca(2+)-permeable cation channel and performs diverse cellular functions. TRPM2 channels are activated by ADP-ribose (ADPR), Ca(2+), H2O2 and other reactive oxygen species (ROS). It is established that TRPM2 serves as a cellular sensor for oxidative stress, mediating oxidative stress-induced [Ca(2+)]i increase and contributing to pathological processes in many cell types. Accumulating evidence has indicated that TRPM2 is a potential therapeutic target for oxidative stress-related diseases. This review will highlight recent progress in this field.
Adenosine Diphosphate Ribose ; metabolism ; Calcium ; physiology ; Calcium Channels ; physiology ; Humans ; Hydrogen Peroxide ; metabolism ; Oxidative Stress ; Reactive Oxygen Species ; metabolism ; TRPM Cation Channels ; physiology

OBJECTIVETo observe the effect of salvianolic acid B (SalB) on high energy phosphate and activity of ATPase of cerebral ischemia in mice, and to study the role of SalB on hydrocephalus further.

METHODNIH mice were divided into four groups randomly: Sham-operated group, cerebral ischemia group, SalB-treated group and Nimodipine (Nim)-collated group. In Sal B-treated group, mice were injected with SalB (22.5 mg x kg(-1)) in vena caudalis at 30 min before the experiment. In Nim-collated group, Nim (0.03 mg x kg(-1)) was injected into tail vein at the same time, while the mice in Sham-operated group and cerebral ischemia group were injected the same volume normal saline. The acute cerebral ischemia model was established by ligating bilateral common carotid arteries for 30 min in mice, then the mice were killed and the content of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), phosphocreatine (PCr) were observed, and the cerebral energy charge (EC) was computed. At the same time, activity of Na(+) -K(+) -ATPase and Ca2(+) -ATPase, content of water in brain tissue were measured.

RESULTCompared with cerebral ischemia group, EC and content of ATP, ADP, PCr in SalB-treated group heightened evidently (P < 0.01). Moreover, activity of Na(+)-K+ ATPase and Ca2+ ATPase in SalB-treated group had a remarkable increase (P < 0.01). But the content of water in brain tissue decreased markedly (P < 0.05).

CONCLUSIONThe mechanism that SalB can relieve content of water in brain tissue of cerebral ischemia in mice, may be associated with improving the content of high-energy phosphoric acid compounds and enhancing the activity of ATPase.

Adenosine Diphosphate ; metabolism ; Adenosine Monophosphate ; metabolism ; Adenosine Triphosphatases ; metabolism ; Adenosine Triphosphate ; metabolism ; Animals ; Benzofurans ; isolation & purification ; pharmacology ; Brain ; drug effects ; metabolism ; pathology ; Brain Ischemia ; physiopathology ; Calcium-Transporting ATPases ; metabolism ; Energy Metabolism ; drug effects ; Male ; Mice ; Phosphocreatine ; metabolism ; Plants, Medicinal ; chemistry ; Random Allocation ; Salvia miltiorrhiza ; chemistry ; Sodium-Potassium-Exchanging ATPase ; metabolism ; Water ; metabolism

OBJECTIVETo investigate the effect of Shuangshen Ningxin (SSNX) formula on energy metabolism of myocardial ischemia/reperfusion rats.

METHODThe myocardial ischemia/reperfusion model of Wistar rats was established through the ligation of left anterior descending branch of coronary artery of for 40 min and the reperfusion for 2 h. The Wistar rats were randomly divided into six groups: the sham operation group, the model group, the Trimetazidine group (10 mg x kg(-1)) and SSNX groups (22.5, 45, 90 mg x kg(-1)). Preventive administration was conducted for 5 d. The operation was performed at 1 h on the day of the last administration. CK-MB assay kit was adopted to detect the activity of serum CK-MB. HPLC was used to determine ATP, ADP and AMP contents in myocardial tissues and calculate TAN and EC.

RESULTThe preventive administration with SSNX could reduce the activity of serum CK-MB and increase ATP content and EC level in myocardial tissues (P < 0.01 or P < 0.05 vs. the model group).

CONCLUSIONSSNX formula can maintain energy charge in cardiomyocytes and relieve ischemia/reperfusion injury by preserving ischemic myocardium ATP.

Adenosine Diphosphate ; metabolism ; Adenosine Monophosphate ; metabolism ; Animals ; Creatine Kinase, MB Form ; blood ; Drugs, Chinese Herbal ; administration & dosage ; Energy Metabolism ; drug effects ; Humans ; Male ; Myocardial Ischemia ; drug therapy ; metabolism ; surgery ; Myocardial Reperfusion ; Rats ; Rats, Wistar

BACKGROUNDPhosphorous magnetic resonance spectroscopy ((31)P-MRS) has been successfully applied to study intracellular membrane compounds and high-energy phosphate metabolism. This study aimed to evaluate the capability of dynamic (31)P-MRS for assessing energy metabolism and mitochondrial function in skeletal muscle from type 2 diabetic patients.

METHODSDynamic (31)P-MRS was performed on 22 patients with type 2 diabetes and 26 healthy volunteers. Spectra were acquired from quadriceps muscle while subjects were in a state of rest, at exercise and during recovery. The peak areas of inorganic phosphate (Pi), phosphocreatine (PCr), and adenosine triphosphate (ATP) were measured. The concentration of adenosine diphosphate (ADP) and the intracellular pH value were calculated from the biochemistry reaction equilibrium. The time constant and recovery rates of Pi, PCr, and ADP were analyzed using exponential curve fitting.

RESULTSAs compared to healthy controls, type 2 diabetes patients had significantly lower skeletal muscle concentrations of Pi, PCr and β-ATP, and higher levels of ADP and Pi/PCr. During exercise, diabetics experienced a significant Pi peak increase and PCr peak decrease, and once the exercise was completed both Pi and PCr peaks returned to resting levels. Quantitatively, the mean recovery rates of Pi and PCr in diabetes patients were (10.74 ± 1.26) mmol/s and (4.74 ± 2.36) mmol/s, respectively, which was significantly higher than in controls.

CONCLUSIONSNon-invasive quantitative (31)P-MRS is able to detect energy metabolism inefficiency and mitochondrial function impairment in skeletal muscle of type 2 diabetics.

Adenosine Diphosphate ; analysis ; Adenosine Triphosphate ; analysis ; Adult ; Diabetes Mellitus, Type 2 ; metabolism ; Female ; Humans ; Magnetic Resonance Spectroscopy ; methods ; Male ; Middle Aged ; Mitochondria, Muscle ; metabolism ; Muscle, Skeletal ; metabolism ; Phosphates ; analysis ; Phosphocreatine ; analysis ; Phosphorus ; chemistry

OBJECTIVETo investigate the effect of benzo(a)pyrene (BaP) on platelet aggregation and expression of P-selectin.

METHODSBlood samples were collected from healthy volunteers and the platelets was washed. Platelet aggregation was monitored by aggregometer and the expression of P-seletin was detected by whole blood flow cytometry.

RESULTBaP (10 μmol/L, 1 μmol/L and 0.1 μmol/L) did not induce platelet aggregation; however, preincubation with BaP (10 μmol/L) significantly enhanced ADP-induced platelet aggregation (P < 0.01) and platelet aggregation was (80 ± 10)%, while BaP-preincubation failed to enhance platelet aggregation under collagen and thrombin stimulation. Flow cytometry showed that preincubation with BaP increased ADP-induced, but not thrombin-induced P-selectin expression (P < 0.01).

CONCLUSIONBaP can stimulate ADP-induced platelet aggregation and P-selectin expression, probably through the interaction with ADP-mediated signal pathway.

Adenosine Diphosphate ; pharmacology ; Benzo(a)pyrene ; pharmacology ; Blood Platelets ; drug effects ; metabolism ; Collagen ; pharmacology ; Humans ; P-Selectin ; blood ; drug effects ; Platelet Aggregation ; drug effects ; Thrombin ; pharmacology