| Full text | |
| Author(s): |
Keppeke, Gerson Dierley
[1, 2]
;
John Calise, S.
[1]
;
Chan, Edward K. L.
[1]
;
Andrade, Luis Eduardo C.
[2, 3]
Total Authors: 4
|
| Affiliation: | [1] Univ Florida, Dept Oral Biol, Gainesville, FL 32610 - USA
[2] Univ Fed Sao Paulo, Div Rheumatol, BR-04023062 Sao Paulo, SP - Brazil
[3] Fleury Med & Hlth Labs, Div Immunol, BR-04102050 Sao Paulo, SP - Brazil
Total Affiliations: 3
|
| Document type: | Journal article |
| Source: | JOURNAL OF GENETICS AND GENOMICS; v. 42, n. 6, p. 287-299, JUN 20 2015. |
| Web of Science Citations: | 19 |
| Abstract | |
Inhibition of guanosine triphosphate (GTP) and cytidine triphosphate (CTP) biosynthetic pathways induces cells to assemble rod/ring (RR) structures, also named cytoophidia, which consist of the enzymes cytidine triphosphate synthase (CTPS) and inosine-5'-monophosphate dehydrogenase 2 (IMPDH2). We aim to explore the interaction of CTPS and IMPDH2 in the generation of RR structures. HeLa and COS-7 cells were cultured in normal conditions or in the presence of 6-diazo-5-oxo-L-norleucine (DON), ribavirin, or mycophenolic acid (MPA). Over 90% of DON-treated cells presented RR structures. In HeLa cells, 35% of the RR structures were positive for IMPDH2 alone, 26% were CTPS alone, and 31% were IMPDH2/CTPS mixed, while in COS-7 cells, 42% of RR were IMPDH2 alone, 41% were CTPS alone, and 10% were IMPDH2/CTPS mixed. Ribavirin and MPA treatments induced only IMPDH2-based RR. Cells were also transfected with an N-terminal hemagglutinin (NHA)-tagged CTPS1 construct. Over 95% of NHA-CTPS1 transfected cells with DON treatment presented IMPDH2-based RR and almost 100% presented CTPS1-based RR; when treated with ribavirin, over 94% of transfected cells presented IMPDH2-based RR and 37% presented CTPS1-based RR, whereas 2% of untreated transfected cells presented IMPDH2-based RR and 28% presented CTPS1-based RR. These results may help in understanding the relationship between CTP and GTP biosynthetic pathways, especially concerning the formation of filamentous RR structures. (AU) | |
| FAPESP's process: | 11/12448-0 - Antibodies anti-"Rods & Rings", HCV and ribavirin/interferon: A human model of autoantibodies generation. |
| Grantee: | Gerson Dierley Keppeke |
| Support Opportunities: | Scholarships in Brazil - Doctorate |