Abstract:
:Sulfated polymannuroguluronate (SPMG) has entered the phase II clinical trial as the first anti-AIDS drug candidate in China. Herein, we report that SPMG was effective at protecting T lymphocytes against apoptosis. Further studies indicated that SPMG significantly elevated mitochondrial membrane potential (MMP) of T cells; inhibited mitochondrial release of cytochrome c (cyto c) in T cells; enhanced the activities of mitochondrial enzyme complex I, III, and V; and subsequently increased ATP level and ATP/ADP ratio. In addition, SPMG potently suppressed reactive oxygen species (ROS) generation in mitochondria at cellular level and scavenged free radicals in cell-free system. The molecular mechanism underlying the ATP-involved and ROS-dependent antiapoptosis of SPMG is characterized as having been caused by its engagement with mitochondrial import receptor and ADP/ATP carrier in T-cell outer and inner mitochondrial membrane, respectively. All these might shed new light on the understanding of anti-AIDS functions of SPMG by protecting T cells of persons infected with human immunodeficiency virus.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Miao B,Li J,Fu X,Gan L,Xin X,Geng Mdoi
10.1124/mol.105.015412keywords:
subject
Has Abstractpub_date
2005-12-01 00:00:00pages
1716-27issue
6eissn
0026-895Xissn
1521-0111pii
mol.105.015412journal_volume
68pub_type
杂志文章abstract::There are now several examples of single G protein-coupled receptors to which binding of specific agonists causes differential effects on the associated signaling pathways. The dopamine D(2) receptor is of special importance because the selective activation of functional pathways has been shown both in vitro and in si...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.66.1.97
更新日期:2004-07-01 00:00:00
abstract::Matrix metalloproteinases (MMPs) are synthesized in response to diverse stimuli, including cytokines, growth factors, hormones, and oxidative stress. Here we show that the nitric oxide (NO) donor 2-(N,N-diethylamino)-diazenolate-2-oxide (DEA-NO) and NO from murine macrophages transcriptionally regulate MMP-13 expressi...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.62.4.927
更新日期:2002-10-01 00:00:00
abstract::Glutathione-S-transferase-catalyzed conjugation of glutathione (GSH) to aflatoxin B1-8,9-epoxide plays an important role in preventing binding of this ultimate carcinogen to target macromolecules. Once formed, the aflatoxin B1-epoxide-GSH conjugates are actively extruded from the cell by an unidentified ATP-dependent ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.51.6.1034
更新日期:1997-06-01 00:00:00
abstract::Catecholamine transporters constitute the biological targets for several important drugs, including antidepressants, cocaine, and related compounds. Some information exists about discrete domains of these transporters that are involved in substrate translocation and uptake blockade, but delineation of domains mediatin...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.58.6.1404
更新日期:2000-12-01 00:00:00
abstract::It has been suggested that elevated cytosolic free calcium plays a key role in acetaminophen-induced cell death. The present study has examined the effect of a toxic concentration of acetaminophen on cytosolic free calcium in single mouse hepatocytes, using the dye fura-2 and video imaging fluorescence microscopy. Cyt...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1992-04-01 00:00:00
abstract::GABAA receptors are predominantly composed of alphabetagamma and alphabetadelta isoforms in the brain. It has been proposed that alphabetagamma receptors mediate phasic inhibition, whereas alphabetadelta receptors mediate tonic inhibition. Propofol (2,6-di-isopropylphenol), a widely used anesthetic drug, exerts its ef...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.104.003426
更新日期:2004-12-01 00:00:00
abstract::Binding by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to the Ah receptor leads to transcriptional activation of several genes and a toxicity syndrome that includes tumor promotion, wasting, hormonal and immune system dysfunction, and death. Recent findings indicate that TCDD may also affect cardiac function. Here, we ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1993-12-01 00:00:00
abstract::An opioid-like receptor has been cloned by several groups of researchers and recently shown to be activated by an endogenous heptadecapeptide termed orphanin FQ (or nociceptin). We isolated the corresponding mouse cDNA and coexpressed it in Xenopus laevis oocytes with the potassium channel subunits Kir3.1 (GIRK1) and ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1996-09-01 00:00:00
abstract::We have cloned new 5-Hydroxytryptamine 4 (5-HT4) receptor splice variants from mouse (m5-HT4(e)R and m5-HT4(f)R), rat (r5-HT4(e)R), and human brain tissue (h5-HT4(e)R) which differ, as do the previously described 5-HT4 receptor variants, in the length and composition of their intracellular C termini after the common s...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1999-05-01 00:00:00
abstract::Neuromedin U (NmU) is a 25 amino acid peptide prominently expressed in the upper gastrointestinal (GI) tract and central nervous system. It is highly conserved throughout evolution and induces smooth muscle contraction in a variety of species. Our understanding of NmU biology has been limited because the identity of i...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.58.4.870
更新日期:2000-10-01 00:00:00
abstract::Wild-type p53 is frequently mutated in late-stage ovarian cancer and has been proposed as a determinant of cisplatin chemosensitivity. We have therefore established a human ovarian cancer cell line differing only in p53 status and characterized its response after treatment with different platinum complexes. The wild-t...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.57.3.503
更新日期:2000-03-01 00:00:00
abstract::Regulators of G-protein signaling (RGS) proteins are important components of signal transduction pathways initiated through G-protein-coupled receptors (GPCRs). RGS proteins accelerate the intrinsic GTPase activity of G-protein alpha-subunits (Galpha) and thus shorten the time course and reduce the magnitude of G-prot...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.106.028670
更新日期:2007-01-01 00:00:00
abstract::Mitsuya and Broder [Proc. Natl. Acad. Sci. USA 83:1911-1915 (1986)] demonstrated that every purine (adenosine, guanosine, and inosine) and pyrimidine (cytidine and thymidine) nucleoside containing the 2',3'-dideoxyribose configuration, when evaluated against human immunodeficiency virus (HIV) in vitro, significantly s...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1988-10-01 00:00:00
abstract::The ADP-sensitive and K+ -sensitive phosphorylated forms of Na,K-ATPase (E1P and E2P, respectively) are believed to be the main phosphorylated intermediates of Na,K-ATPase. In the presence of 100 mM Na+, E2P is the major component of the phosphorylated form in all native Na,K-ATPase preparations known, including the m...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1982-11-01 00:00:00
abstract::Activation of muscarinic cholinergic receptors of 1321N1 human astrocytoma cells attenuates cyclic AMP accumulation. This effect results from an activation of phosphodiesterase with no direct inhibition of adenylate cyclase activity. In spite of this lack of coupling of muscarinic receptors to adenylate cyclase, guani...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1985-01-01 00:00:00
abstract::Guanine nucleotide-binding proteins (G proteins) transduce signals from agonist- and light-sensitive receptors. In the visual excitation system, the photon receptor rhodopsin is coupled to the G protein Gt (transducin). Gt is composed of alpha, beta, and gamma subunits; the alpha subunit binds guanine nucleotide, wher...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1990-06-01 00:00:00
abstract::The N-methyl-D-aspartate (NMDA)-sensitive glutamate receptors are known to be inhibited by 3-amino-1-hydroxy-2-pyrrolidone (HA-966) and 7-chlorokynurenic acid (Cl-KYN), which act at the glycine-regulated allosteric modulatory center. In this work we show that, in synaptic membranes prepared from rat brain, Cl-KYN and ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1989-12-01 00:00:00
abstract::Activation of synthesis-modulating dopamine autoreceptors by dopamine or its agonists has been shown to inhibit dopamine synthesis in the rat striatum. However, systemic administration of the direct-acting dopamine agonist apomorphine failed to inhibit dopamine synthesis in striata from rats that had received local un...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1988-12-01 00:00:00
abstract::Stimulation of beta2-adrenoceptors with the selective beta2 agonist procaterol caused a biphasic decrease in cell surface M2 muscarinic receptor number in human embryonic lung 299 cells when measured with the hydrophilic antagonist [3H]N-methylscopolamine. In contrast, total muscarinic receptor number, measured with t...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1996-04-01 00:00:00
abstract::Mitochondrial disorders are devastating genetic diseases for which efficacious therapies are still an unmet need. Recent studies report that increased availability of intracellular NAD obtained by inhibition of the NAD-consuming enzyme poly(ADP-ribose) polymerase (PARP)-1 or supplementation with the NAD-precursor nico...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.114.097204
更新日期:2015-06-01 00:00:00
abstract::We examined the influence of the molecular structure of four novel adamantane derivatives on their ability to block the channels of nicotinic acetylcholine (ACh) and N-methyl-D-aspartate (NMDA) receptors. The structure of the drugs is Ad-CH2-N+H2-(CH2)5-R, where Ad is adamantane and R was varied from ammonium (IEM-175...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1995-03-01 00:00:00
abstract::n-Dodecylguanidine (C12-G) is an amphipathic compound with a guanidine moiety, which is positively charged at physiological pH, and a hydrophobic side chain. Its effects on an A-type K+ channel clone (rKv1.4) expressed in Xenopus oocytes were examined. C12-G caused a concentration-dependent (1-20 microM) positive shif...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1995-07-01 00:00:00
abstract::Increasing evidence implicates apoptosis as a major mechanism of cell death in methamphetamine (METH) neurotoxicity. The involvement of a neuroimmune component in apoptotic cell death after injury or chemical damage suggests that cytokines may play a role in METH effects. In the present study, we examined if the absen...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.58.6.1247
更新日期:2000-12-01 00:00:00
abstract::α-Conotoxins are subtype-selective nicotinic acetylcholine receptor (nAChR) antagonists. Although potent α3β2 nAChR-selective α-conotoxins have been identified, currently characterized α-conotoxins show no or only weak affinity for α4β2 nAChRs, which are, besides α7 receptors, the most abundant nAChRs in the mammalian...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.112.078683
更新日期:2012-10-01 00:00:00
abstract::Combining chemotherapeutics to treat malignant tumors has been shown to be effective in preventing drug resistance, tumor recurrence, and reducing tumor size. We modeled combination drug therapy in PC-3 human prostate cancer cells using mixture design response surface methodology (MDRSM), a statistical technique desig...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.117.111450
更新日期:2018-08-01 00:00:00
abstract::The antiherpetic agent (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) was found to be an efficient substrate for recombinant Drosophila melanogaster-deoxyribonucleoside kinase with a K(m) of 4.5 microM and a V(max) of 400 nmol/microg protein/h compared with 1.3 microM and 62.5 nmol/microg protein/h, respectively, for the...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.57.4.811
更新日期:2000-04-01 00:00:00
abstract::The small GTPase Rac1 has been widely implicated in mammary tumorigenesis and metastasis. Previous studies established that stimulation of ErbB receptors in breast cancer cells activates Rac1 and enhances motility via the Rac-guanine nucleotide exchange factor P-Rex1. As the Janus tyrosine kinase 2 (Jak2)/signal trans...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.112.084293
更新日期:2013-05-01 00:00:00
abstract::Past decades of cancer research have mainly focused on the role of various extracellular and intracellular biochemical signals on cancer progression and metastasis. Recent studies suggest an important role of mechanical forces in regulating cellular behaviors. This review first provides an overview of the mechanobiolo...
journal_title:Molecular pharmacology
pub_type: 杂志文章,评审
doi:10.1124/mol.116.106765
更新日期:2016-12-01 00:00:00
abstract::The human histamine H(4)-receptor (hH(4)R) possesses high constitutive activity and, like the human H(1)-receptor (hH(1)R), is involved in the pathogenesis of type-I allergic reactions. The study aims were to explore the value of dual H(1)/H(4)R antagonists as antiallergy drugs and to address the question of whether H...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.109.058651
更新日期:2009-11-01 00:00:00
abstract::We describe the nucleic acid sequence encoding a human 5-hydroxytryptamine1D (5-HT1D) serotonin receptor and some of the functional characteristics of the gene product. The receptor gene was isolated by hybridization to a probe based on a canine thyroid cDNA (called RDC4) previously isolated by others and believed to ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1991-08-01 00:00:00