The mechanism of 3'-azido-2',3'-dideoxythymidine resistance to human lymphoid cells
The human T-lymphoid cell line H9 resistant to 3'-azido-2',3'-dideoxythymidine (AZT) has a very low level of thymidine kinase (TK) expression which accounts for the failure of AZT to inhibit HIV-1 replication. In the present study DNA methylation and histone deacetylation as possible mechanisms of decreased TK gene expression in the resistant cells were investigated. The resistant cells expressed high levels of DNA methyltransferases (DNMTs) 3a and 3b. The DNA methylation inhibitor, 5-aza-cytidine (5-aza-C), increased TK gene expression and antiviral activity of AZT in the resistant cells, while histone deacetylase inhibitor trichostatin A (TSA) had no effect. The results suggest that hypermethylation of the TK gene but not histone deacetylation in AZT-resistant H9 cells accounts for decreased TK gene expression and failure of AZT to inhibit HIV-1 replication probably due to overexpression of DNMT 3a and 3b.
| Medienart: |
Artikel |
|---|
| Erscheinungsjahr: |
2003 |
|---|---|
| Erschienen: |
2003 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
|---|---|
| Enthalten in: |
International journal of molecular medicine - 11(2003), 6 vom: 08. Juni, Seite 743-7 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Hoever, Gerold [VerfasserIn] |
|---|
| Anmerkungen: |
Date Completed 26.02.2004 Date Revised 03.12.2021 published: Print Citation Status MEDLINE |
|---|
| Förderinstitution / Projekttitel: |
|
|---|
| PPN (Katalog-ID): |
NLM125053037 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM125053037 | ||
| 003 | DE-627 | ||
| 005 | 20231222204903.0 | ||
| 007 | tu | ||
| 008 | 231222s2003 xx ||||| 00| ||eng c | ||
| 028 | 5 | 2 | |a pubmed24n0417.xml |
| 035 | |a (DE-627)NLM125053037 | ||
| 035 | |a (NLM)12736716 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Hoever, Gerold |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The mechanism of 3'-azido-2',3'-dideoxythymidine resistance to human lymphoid cells |
| 264 | 1 | |c 2003 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 500 | |a Date Completed 26.02.2004 | ||
| 500 | |a Date Revised 03.12.2021 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The human T-lymphoid cell line H9 resistant to 3'-azido-2',3'-dideoxythymidine (AZT) has a very low level of thymidine kinase (TK) expression which accounts for the failure of AZT to inhibit HIV-1 replication. In the present study DNA methylation and histone deacetylation as possible mechanisms of decreased TK gene expression in the resistant cells were investigated. The resistant cells expressed high levels of DNA methyltransferases (DNMTs) 3a and 3b. The DNA methylation inhibitor, 5-aza-cytidine (5-aza-C), increased TK gene expression and antiviral activity of AZT in the resistant cells, while histone deacetylase inhibitor trichostatin A (TSA) had no effect. The results suggest that hypermethylation of the TK gene but not histone deacetylation in AZT-resistant H9 cells accounts for decreased TK gene expression and failure of AZT to inhibit HIV-1 replication probably due to overexpression of DNMT 3a and 3b | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Anti-HIV Agents |2 NLM | |
| 650 | 7 | |a DNA, Complementary |2 NLM | |
| 650 | 7 | |a DNMT3A protein, human |2 NLM | |
| 650 | 7 | |a Histones |2 NLM | |
| 650 | 7 | |a Zidovudine |2 NLM | |
| 650 | 7 | |a 4B9XT59T7S |2 NLM | |
| 650 | 7 | |a DNA Modification Methylases |2 NLM | |
| 650 | 7 | |a EC 2.1.1.- |2 NLM | |
| 650 | 7 | |a DNA Methyltransferase 3A |2 NLM | |
| 650 | 7 | |a EC 2.1.1.37 |2 NLM | |
| 650 | 7 | |a Thymidine Kinase |2 NLM | |
| 650 | 7 | |a EC 2.7.1.21 |2 NLM | |
| 700 | 1 | |a Groeschel, Bettina |e verfasserin |4 aut | |
| 700 | 1 | |a Chandra, Prakash |e verfasserin |4 aut | |
| 700 | 1 | |a Doerr, Hans W |e verfasserin |4 aut | |
| 700 | 1 | |a Cinatl, Jindrich |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t International journal of molecular medicine |d 1998 |g 11(2003), 6 vom: 08. Juni, Seite 743-7 |w (DE-627)NLM097489425 |x 1791-244X |7 nnns |
| 773 | 1 | 8 | |g volume:11 |g year:2003 |g number:6 |g day:08 |g month:06 |g pages:743-7 |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 11 |j 2003 |e 6 |b 08 |c 06 |h 743-7 | ||