Smac is a mitochondrial protein that interacts with inhibitor of apoptosis proteins (IAPs). Upon apoptotic stimuli, the Smac is released into the cytoplasm to inhibit the capase-binding activity of IAPs. The low expression of Smac in tissues has been reported existing in various cancers. Smac plays key roles in prognosis and chemoradiotherapy resistance of malignant tumor besides neoplasm genesis and growth. Furthermore, Smac may be a molecular therapeutic target in cancer patients. Overexpression of Smac by transfecting extrinsic Smac gene or Smac mimetic into tumor cell can improve their sensitivity to radiotherapy and chemotherapy, which has great significance to the treatment of tumor. Our review will focus on the roles of Smac in structure, pro-apoptotic mechanism, tissue distribution and cancer treatment.
Humans ; Intracellular Signaling Peptides and Proteins ; chemistry ; metabolism ; physiology ; Mitochondrial Proteins ; chemistry ; metabolism ; physiology ; Neoplasms ; therapy ; Tissue Distribution

Na(+)-H(+) exchangers (NHE) are major membrane proteins that have been identified as signal transduction mediators in the regulation of cell differentiation and important membrane ion transporters in the regulation of the intercellular pH and the cell volume. NHE are composed of at least six isoforms and activated in growth factor-regulated cell differentiation. However, little is known about the differential regulation of NHE expression in the development. In the present study, we studied developmental regulation of the expression of NHE isoforms in human fetal tissues by comparing the expression of various isoforms between two developmental stages, i.e., week 11 (11 W) and week 16 (16 W). The results demonstrated that NHE1 transcripts were expressed ubiquitously. In comparison to the expression at 16 W, the level of NHE1 transcripts was low and varied significantly in a tissue-specific pattern at 11 W, suggesting that the house-keeping function of MHE1 occurs at 11 W or earlier and becomes well established at least as early as at 16 W. The tissue-specifically restricted expression of NHE2 and NHE3 was regulated at 11 W and 16 W in an opposite tendency, supporting the overlapping relationship between NHE2 and NHE3 in the tissue distribution as reported in adults. NHE5 expression was relatively ubiquitous at 11 W and became restricted in the cerebellum at 16 W, suggesting that the restrictive expression of NHE5 in the brain occurs later than that of other isoforms. The present study demonstrates a space time-dependent regulation of the tissue-specific expression pattern of NHE isoforms during human development between 11 W and 16 W. The results also suggest that at 16 W or earlier the expression pattern of developing tissues becomes similar to that of adult tissues. The observed developmental regulation of NHE expression provides a molecular basis for further study of the function and regulation of NHE gene during development.
Fetus ; embryology ; metabolism ; Gene Expression Regulation, Developmental ; physiology ; Humans ; Organ Specificity ; Protein Isoforms ; metabolism ; physiology ; RNA, Messenger ; metabolism ; physiology ; Sodium-Hydrogen Exchangers ; metabolism ; physiology ; Tissue Distribution

The placenta is an essential organ that synthesizes several growth and angiogenic factors for its own growth as well as fetal development. It is known that the placenta growth factor (PlGF)is a member of the vascular endothelial growth factor family and is critical for placental growth and fetal development. However, there is little information regarding the expression pattern and cellular localization of PlGF mRNA in rat placenta during pregnancy. The aim of this study was to define the distribution of PlGF mRNA in rat placenta at various gestations. RT-PCR analysis showed that the expression level of PlGF mRNA increased as gestation advanced. Using in situ hybridization histochemistry, positive cells of PlGF mRNA were detected in chorionic villi. PlGF mRNA was expressed in the trophoblast cells and stroma cells surrounding the blood vessels within chorionic villi on day 13 and 15. Also, positive signals of PlGF mRNA were strongly detected in stroma cells of chorionic villi on day 17, 19, and 21. In particular, the density and number of positive signals of PlGF mRNA was significantly increased as gestation advanced. The expression pattern of PlGF mRNA in rat placenta during pregnancy demonstrates that PlGF plays a functional role for placental growth and fetal development during mid-late pregnancy.
Animals ; Female ; Gene Expression Regulation/physiology ; Placenta/*metabolism ; Pregnancy ; Pregnancy Proteins/*metabolism ; RNA, Messenger/*metabolism ; Rats ; Rats, Sprague-Dawley ; Tissue Distribution/physiology

Animals ; Atherosclerosis ; etiology ; metabolism ; Gene Expression Regulation ; Humans ; Lipase ; analysis ; genetics ; physiology ; Lipoproteins ; metabolism ; Lipoproteins, HDL ; metabolism ; Lipoproteins, LDL ; metabolism ; Polymorphism, Genetic ; Tissue Distribution

OBJECTIVETo observe the effect of fibrous capsule to prevent the flexor tendon adhesion.

METHODSSix bum patients with 33 digits were treated with the fibrous capsule of the expanded flaps which was used to wrap the exposed flexor tendon in zone III in order to prevent the flexor tendon adhesion.

RESULTSFrom 1999-2001 ,all of the patients were followed up to 1-3 years. The functions, assessed with the TAM method, were excellent in 18 digits, fair in three and poor in one. The excellent and good rate was 87.88%.

CONCLUSIONThe fibrous capsule could be used to prevent or reduce the tendon adhesion.

Adult ; Burns ; rehabilitation ; surgery ; Female ; Head ; physiology ; surgery ; Humans ; Male ; Muscles ; surgery ; Surgical Flaps ; supply & distribution ; Surgical Procedures, Operative ; methods ; Tendons ; surgery ; Tissue Adhesions ; prevention & control ; Treatment Outcome

We developed a method that allows us to label nociceptive neurons innervating tooth-pulp in rat trigeminal ganglion neurons using a retrograde fluorescence-tracing method, to record ATP-activated current in freshly isolated fluorescence-labeled neurons and to conduct single cell immunohistochemical staining for P2X1 and P2X3 subunits in the same neuron. Three types of ATP-activated current in these neurons (F, I and S) were recorded. The cells exhibiting the type F current mainly showed positive staining for P2X3, but negative staining for P2X1. The results provide direct and convincing evidence at the level of single native nociceptive neurons for correlation of the characteristics of ATP-activated currents with their composition of P2X1 and P2X3 subunits and cell size. The results also suggest that the P2X3, but not P2X1, is the main subunit that mediates the fast ATP-activated current in nociceptive neurons.
Action Potentials ; physiology ; Adenosine Triphosphate ; metabolism ; Animals ; Dental Pulp ; innervation ; physiology ; Nociceptors ; cytology ; physiology ; Rats ; Rats, Sprague-Dawley ; Receptors, Purinergic P2X1 ; metabolism ; Receptors, Purinergic P2X3 ; metabolism ; Tissue Distribution ; Trigeminal Nerve ; cytology ; metabolism

Proliferation of vascular smooth muscle cells (VSMCs) is often accompanied by changes in intracellular actin distribution. The changes are controlled by the signal transduction pathways of protein kinase C/mitogenic activated protein kinase (PKC-MAPK), but the mechanism is unclear. In order to study the effect of insulin on the intracellular signal transduction (PKC-MAPK) probably involved in the modulation of proliferation and redistribution of actins in the VSMCs, the DNA synthesis, MAPK activities and its gene expression, and the redistribution of intracellular actins were investigated in the isolated VSMCs of SHR pretreated with PKC inhibitor and/or insulin, respectively. We found that insulin treatment resulted in proliferation of the VSMCs and an increase in [(3)H] TdR incorporation. Meanwhile, the activities and expression of MAPK increased significantly compared to the control group. These effects of insulin were blocked by PKC inhibitor. In addition, insulin caused a redistribution of the intracellular actins in VSMCs, which was also inhibited by PKC inhibitor. It is, therefore, suggested that these effects of insulin on VSMCs proliferation and distribution of the intracellular actins may be mediated by the MAPK signal transduction pathway.
Actins ; metabolism ; Animals ; Cell Division ; drug effects ; In Vitro Techniques ; Insulin ; pharmacology ; Mitogen-Activated Protein Kinases ; physiology ; Muscle, Smooth, Vascular ; cytology ; Myocytes, Smooth Muscle ; drug effects ; enzymology ; metabolism ; Protein Kinase C ; physiology ; Rats ; Rats, Inbred SHR ; Tissue Distribution

OBJECTIVETo examine the effect of body fat mass and fat distribution on pulmonary ventilatory function among the adult females.

METHODSBased on the multistage cluster sampling principal, we selected 935 healthy adult females with ages of 19-81 years old in Heilongjiang province to conduct the study. Every 10-years old as a age group. Firstly obtain the basic situation through the questionnaire survey, and then measure the height, body weight, waistline, hip circumference, body composition and lung function. FVC, FEV1, PEF, FEF25%, FEF 50%, FEF 75% and MMEF were determined. This study also examined the relationships between percentage body fat (PBF), waist-hip ratio (WHR) and FVC, FEV1, PEF, FEF25%, FEF 50%, FEF 75%, MMEF.

RESULTSPBF of subjects with ages of 19 - 29 years old and over 60 years old were (16.89 ± 5.34)% and (24.39 ± 6.83)%, WHR were 0.77 ± 0.05 and 0.88 ± 0.06, respectively. PBF and WHR tended to increase with age (F = 50.11, P value < 0.01). PBF obesity rates of subjects with ages of 19 - 29 years old and over 60 years old were 3.23% (7/217) and 43.75% (28/64), WHR obesity rates were 19.35% (42/217) and 85.94% (55/64) respectively. PBF obesity rate and WHR obesity rate tended to increase with age (χ(2) = 161.66, P value < 0.01; χ(2) = 159.61, P value < 0.01). PBF obesity groups compared with the normal groups, the former pulmonary ventilation function reduced significantly, of which FEF 50%, FEF 75% and MMEF decreased 2.61%, 19.44%, 10.28%, respectively. WHR obesity groups compared with the normal groups, the former pulmonary ventilation function reduced significantly, of which FEF 50%, FEF 75% and MMEF decreased 7.61%, 23.15%, 12.04%. After adjustment of age, height and body mass index (BMI), PBF was negatively correlated with FVC, FEV1, PEF and FEF25% (r values were -0.14, -0.14, -0.07, -0.07, respectively, all P value s < 0.05); WHR was negatively correlated with FEV1 (r value was -0.07, P value < 0.05) after adjustment of age, height and BMI.

CONCLUSIONPBF augmentation and abdominal obesity among adult females may be the risk factors of pulmonary function impairment.

Adipose Tissue ; Adult ; Aged ; Aged, 80 and over ; Body Fat Distribution ; China ; Female ; Humans ; Lung ; physiology ; Middle Aged ; Pulmonary Ventilation ; Risk Factors ; Sampling Studies ; Surveys and Questionnaires ; Waist-Hip Ratio ; Young Adult

Multidrug resistance proteins (MRPs) are members of the C family of a group of proteins named ATP-binding cassette (ABC) transporters. These ABC transporters together form the largest branch of proteins within the human body. The MRP family comprises of 13 members, of which MRP1 to MRP9 are the major transporters indicated to cause multidrug resistance in tumor cells by extruding anticancer drugs out of the cell. They are mainly lipophilic anionic transporters and are reported to transport free or conjugates of glutathione (GSH), glucuronate, or sulphate. In addition, MRP1 to MRP3 can transport neutral organic drugs in free form in the presence of free GSH. Collectively, MRPs can transport drugs that differ structurally and mechanistically, including natural anticancer drugs, nucleoside analogs, antimetabolites, and tyrosine kinase inhibitors. Many of these MRPs transport physiologically important anions such as leukotriene C4, bilirubin glucuronide, and cyclic nucleotides. This review focuses mainly on the physiological functions, cellular resistance characteristics, and probable in vivo role of MRP1 to MRP9.
Antineoplastic Agents ; metabolism ; pharmacology ; Biological Transport ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Glutathione ; metabolism ; Humans ; Leukotriene C4 ; metabolism ; Multidrug Resistance-Associated Proteins ; metabolism ; physiology ; Neoplasms ; drug therapy ; metabolism ; Tissue Distribution

Apoptosis is regulated by interaction of antiapoptotic Bcl-2 family proteins with various proapoptotic proteins, several of which are also members of the Bcl-2 family. BNIP3 (formerly NIP3) is a proapoptotic mitochondrial protein classified in the Bcl-2 family based on limited sequence homology-3 (BH3) domain and COOH-terminal transmembrane domain. Sequence comparison of BNIP3 has indicated that there are several BNIP3 human homologs of this protein, like BNIP3L, Nix and BNIP3. We have cloned a new member of BNIP3 family from the cDNA library prepared from human dermal papilla cells and designated as BNIP3h. BNIP3h shows substantial homology with other BNIP3 family proteins. BNIP3h induced apoptosis from 24 hours after transfection in MCF7 cell lines and its apoptosis inducing activity is extended until 72 hours after transfection.
Amino Acid Sequence ; Apoptosis/*physiology ; Base Sequence ; Cells, Cultured ; Cloning, Molecular ; Dermis/chemistry/cytology ; Human ; Membrane Proteins/chemistry/*genetics/metabolism ; Mitochondria/chemistry ; Molecular Sequence Data ; Multigene Family ; Sequence Alignment ; Tissue Distribution ; Transfection ; Tumor Cells, Cultured