Upregulation of HIV-1 replication in chronically infected cells by ingenol derivatives. 1998

M Fujiwara, and M Okamoto, and K Ijichi, and K Tokuhisa, and Y Hanasaki, and K Katsuura, and D Uemura, and S Shigeta, and K Konno, and T Yokota, and M Baba
Rational Drug Design Laboratories, Fukushima, Japan.

We have previously reported that ingenol derivatives are highly potent inhibitors of human immunodeficiency virus type 1 (HIV-1) replication in acutely infected cells. In this study, however, we have found that some ingenol derivatives strongly enhance the replication of HIV-1 in chronically infected cells at nanomolar concentrations. One of the derivatives could activate nuclear factor kappa B (NF-kappa B), a potent inducer of HIV-1 replication, through the activation of protein kinase C (PKC). Whereas another derivative, which affected neither PKC nor NF-kappa B, significantly enhanced HIV-1 replication, suggesting that a PKC-independent mechanism may also exist in ingenol derivative-induced HIV-1 upregulation.

UI MeSH Term Description Entries
D011493 Protein Kinase C An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. Calcium Phospholipid-Dependent Protein Kinase,Calcium-Activated Phospholipid-Dependent Kinase,PKC Serine-Threonine Kinase,Phospholipid-Sensitive Calcium-Dependent Protein Kinase,Protein Kinase M,Calcium Activated Phospholipid Dependent Kinase,Calcium Phospholipid Dependent Protein Kinase,PKC Serine Threonine Kinase,Phospholipid Sensitive Calcium Dependent Protein Kinase,Phospholipid-Dependent Kinase, Calcium-Activated,Serine-Threonine Kinase, PKC
D002087 Butyrates Derivatives of BUTYRIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxypropane structure. Butyrate,n-Butyrate,Butanoic Acids,Butyric Acids,Acids, Butanoic,Acids, Butyric,n Butyrate
D004224 Diterpenes Twenty-carbon compounds derived from MEVALONIC ACID or deoxyxylulose phosphate. Diterpene,Diterpenes, Cembrane,Diterpenes, Labdane,Diterpenoid,Labdane Diterpene,Norditerpene,Norditerpenes,Norditerpenoid,Cembranes,Diterpenoids,Labdanes,Norditerpenoids,Cembrane Diterpenes,Diterpene, Labdane,Labdane Diterpenes
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014779 Virus Replication The process of intracellular viral multiplication, consisting of the synthesis of PROTEINS; NUCLEIC ACIDS; and sometimes LIPIDS, and their assembly into a new infectious particle. Viral Replication,Replication, Viral,Replication, Virus,Replications, Viral,Replications, Virus,Viral Replications,Virus Replications
D015497 HIV-1 The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte. Human immunodeficiency virus 1,HIV-I,Human Immunodeficiency Virus Type 1,Immunodeficiency Virus Type 1, Human
D015854 Up-Regulation A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins. Receptor Up-Regulation,Upregulation,Up-Regulation (Physiology),Up Regulation
D016328 NF-kappa B Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA. Immunoglobulin Enhancer-Binding Protein,NF-kappa B Complex,Nuclear Factor kappa B,Transcription Factor NF-kB,kappa B Enhancer Binding Protein,Ig-EBP-1,NF-kB,NF-kappaB,Nuclear Factor-Kappab,Complex, NF-kappa B,Enhancer-Binding Protein, Immunoglobulin,Factor NF-kB, Transcription,Factor-Kappab, Nuclear,Ig EBP 1,Immunoglobulin Enhancer Binding Protein,NF kB,NF kappa B Complex,NF kappaB,NF-kB, Transcription Factor,Nuclear Factor Kappab,Transcription Factor NF kB
D016655 HIV Core Protein p24 A major core protein of the human immunodeficiency virus encoded by the HIV gag gene. HIV-seropositive individuals mount a significant immune response to p24 and thus detection of antibodies to p24 is one basis for determining HIV infection by ELISA and Western blot assays. The protein is also being investigated as a potential HIV immunogen in vaccines. HIV Major Core Protein p24,HIV gag Gene Product p24,HIV p24 Antigen,gag Protein p24, HIV,p24(HIV),HIV Protein p24,HTLV-III p24,p24 protein, Human Immunodeficiency Virus,HTLV III p24,p24 Antigen, HIV,p24, HIV Protein,p24, HTLV-III
D017871 Calcium-Calmodulin-Dependent Protein Kinases A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277) Ca(2+)-Calmodulin-Dependent Protein Kinase,Calcium-Calmodulin-Dependent Protein Kinase,Calmodulin-Dependent Protein Kinase,Calmodulin-Dependent Protein Kinases,Multifunctional Calcium-Calmodulin-Dependent Protein Kinase,Restricted Calcium-Calmodulin-Dependent Protein Kinase,Calcium-Calmodulin-Dependent Protein Kinases, Multifunctional,Calcium-Calmodulin-Dependent Protein Kinases, Restricted,Calmodulin-Dependent Multiprotein Kinase,Calmodulin-Kinase,Cam-MPK,Multifunctional Calcium-Calmodulin-Dependent Protein Kinases,Restricted Calcium-Calmodulin-Dependent Protein Kinases,Calcium Calmodulin Dependent Protein Kinase,Calcium Calmodulin Dependent Protein Kinases, Multifunctional,Calcium Calmodulin Dependent Protein Kinases, Restricted,Calmodulin Dependent Multiprotein Kinase,Calmodulin Dependent Protein Kinase,Calmodulin Dependent Protein Kinases,Calmodulin Kinase,Cam MPK,Kinase, Calcium-Calmodulin-Dependent Protein,Kinase, Calmodulin-Dependent Protein,Multifunctional Calcium Calmodulin Dependent Protein Kinase,Multifunctional Calcium Calmodulin Dependent Protein Kinases,Multiprotein Kinase, Calmodulin-Dependent,Protein Kinase, Calcium-Calmodulin-Dependent,Protein Kinase, Calmodulin-Dependent,Protein Kinases, Calcium-Calmodulin-Dependent,Protein Kinases, Calmodulin-Dependent,Restricted Calcium Calmodulin Dependent Protein Kinase,Restricted Calcium Calmodulin Dependent Protein Kinases

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