This panel provides drug-protein interaction and their ADRs along with references
| Toxicity |
Interacting Protein |
Mechanism |
Reference |
| Atp Deficiency Syndrome | ADP/ATP translocator (P05141) | ADP/ATP translocator impairment by AZT as one of the biochemical processes responsible for the ATP deficiency syndrome [ ADR Type 3 ] | 3'-Azido-3'-deoxythmidine uptake into isolated rat liver mitochondria and impairment of ADP/ATP translocator
|
| Cellular Senescence | p14(ARF) (Q8N726) | Inhibition of telomerase activity@progressive telomere shortening and increase p14(ARF) expression@elicit stabilization and reactivation of the tumor suppressor p53-dependent transcription@ increased expression of the cyclin-dependent kinase inhibitor p21(Waf1) and accumulation of p27(kip1)@ thereby inducing cellular senescence and tumor cell death [ ADR Type 1 ] | Persistent inhibition of telomerase reprograms adult T-cell leukemia to p53-dependent senescence
|
| Cellular Senescence | P21 protein (P78460) | Inhibition of telomerase activity@progressive telomere shortening and increase p14(ARF) expression@elicit stabilization and reactivation of the tumor suppressor p53-dependent transcription@ increased expression of the cyclin-dependent kinase inhibitor p21(Waf1) and accumulation of p27(kip1)@ thereby inducing cellular senescence and tumor cell death [ ADR Type 1 ] | Persistent inhibition of telomerase reprograms adult T-cell leukemia to p53-dependent senescence
|
| Cytotoxicity | Cytochrome c oxidase subunit 4 (P13073) | Increase lactate production and decrease activities of COX (complex IV) and SDH (part of complex II)@are the most potent inhibitors of mitochondrial function@thus AZT@ ddI and ddC all exert Cytotoxicity on human muscle cells and induce functional alterations of mitochondria possibly due to mechanisms other than the sole mtDNA depletion [ ADR Type 1 ] | Cellular and mitochondrial toxicity of zidovudine (AZT), didanosine (ddI) and zalcitabine (ddC) on cultured human muscle cells
|
| Cytotoxicity | SDH (Part of complex II) (P56221) | Increase lactate production and decrease activities of COX (complex IV) and SDH (part of complex II)@are the most potent inhibitors of mitochondrial function@thus AZT@ ddI and ddC all exert Cytotoxicity on human muscle cells and induce functional alterations of mitochondria possibly due to mechanisms other than the sole mtDNA depletion. [ ADR Type 1 ] | Cellular and mitochondrial toxicity of zidovudine (AZT), didanosine (ddI) and zalcitabine (ddC) on cultured human muscle cells
|
| Hematopoietic Toxicity | Erythropoietin (P01588) | The effect of erythropoietin (EPO) and interleukin 3 (IL-3), either alone or in combination, on the hematopoietic toxicity associated with zidovudine in vivo, as determined by peripheral blood indices, and assay of hematopoietic progenitors [ ADR Type 5 ] | In-vivo effect of interleukin 3 and erythropoietin, either alone or in combination, on the hematopoietic toxicity associated with zidovudine
|
| Hematopoietic Toxicity | Interleukin-3 (P08700) | The effect of erythropoietin (EPO) and interleukin 3 (IL-3)@ either alone or in combination@ on the hematopoietic toxicity associated with zidovudine in vivo@ as determined by peripheral blood indices@ and assay of hematopoietic progenitors [ ADR Type 5 ] | In-vivo effect of interleukin 3 and erythropoietin, either alone or in combination, on the hematopoietic toxicity associated with zidovudine
|
| Increased Toxicity | Thymidine kinase (P04183) | Activation of the cytosolic thymidine kinase isozyme (TK1) is associated with increased toxicity of ZDV,which is responsible for mitochondrial toxicity is formed in the cytosol [ ADR Type 2 ] | Zidovudine phosphorylation and mitochondrial toxicity in vitro
|
| Mitochondrial Damage | Thymidine kinase 2 mitochondrial (O00142) | The mitochondrial isozyme of thymidine kinase (TK2) plays only a minor part in ZDVMP formation,associated with cytotoxicity, thought to be mediated through mitochondrial damage. [ ADR Type 2 ] | Zidovudine phosphorylation and mitochondrial toxicity in vitro
|
| Mitochondrial Defects | Cytochrome c oxidase (P00395) | A significant decrease in CYTOX activity in heart and RG was evident,indicate that AZT induces mitochondrial defects primarily in muscles with the highest oxidative capacities (heart and RG) [ ADR Type 2 ] | Zidovudine (AZT) induced alterations in mitochondrial biogenesis in rat striated muscles
|
| Mitochondrial Defects | mitochondrial transcription factor A (Q00059) | AZT treatment could alter the expression of the mitochondrial transcription factor A (mtTFA)@ a key molecule involved in mitochondrial DNA (mtDNA) replication and transcription@indicating that AZT induces mitochondrial defects primarily in muscles with the highest oxidative capacities (heart and RG) [ ADR Type 2 ] | Zidovudine (AZT) induced alterations in mitochondrial biogenesis in rat striated muscles
|
| Mitochondrial Defects | Nuclear respiratory factor 1 (Q16656) | Aparent compensatory increase in mtTFA mRNA level that could not be attributed to enhanced transcriptional activation mediated by nuclear respiratory factor 1 (NRF-1)@indicating that AZT induces mitochondrial defects primarily in muscles with the highest oxidative capacities (heart and RG). [ ADR Type 2 ] | Zidovudine (AZT) induced alterations in mitochondrial biogenesis in rat striated muscles
|
| Mitochondrial Toxicity | NADH-cytochrome b5 reductase (P00387) | AZT induced a dose-dependent inhibition of both NADH-linked respiration in intact mitochondria and NADH-cytochrome c reductase activity in freeze-thawed mitochondrial preparations,suggesting its mechanism of mitochondrial toxicity. [ ADR Type 1 ] | AZT causes tissue-specific inhibition of mitochondrial bioenergetic function
|
| Mitochondrial Toxicity | Respiratory enzyme complex I (P00049) | High concentrations of AZT inhibit electron transfer through respiratory enzyme complex I,suggesting its mechanism of mitochondrial toxicity [ ADR Type 2 ] | AZT causes tissue-specific inhibition of mitochondrial bioenergetic function
|
| Mtdna Depletion | DNA-directed RNA polymerase mitochondrial (O00411) | Zidovudine can inhibit mitochondrial (mt)DNA polymerase and cause termination of synthesis of growing mtDNA strands and mtDNA depletion [ ADR Type 1 ] | Cellular and mitochondrial toxicity of zidovudine (AZT), didanosine (ddI) and zalcitabine (ddC) on cultured human muscle cells
|
| Termination Of Synthesis Of Mtdna Strands | DNA-directed RNA polymerase mitochondrial (O00411) | Zidovudine can inhibit mitochondrial (mt)DNA polymerase and cause termination of synthesis of growing mtDNA strands and mtDNA depletion [ ADR Type 1 ] | Cellular and mitochondrial toxicity of zidovudine (AZT), didanosine (ddI) and zalcitabine (ddC) on cultured human muscle cells
|
| Tumor Cell Death | P21 protein (P78460) | Inhibition of telomerase activity@progressive telomere shortening and increase p14(ARF) expression@elicit stabilization and reactivation of the tumor suppressor p53-dependent transcription@ increased expression of the cyclin-dependent kinase inhibitor p21(Waf1) and accumulation of p27(kip1)@ thereby inducing cellular senescence and tumor cell death [ ADR Type 1 ] | Persistent inhibition of telomerase reprograms adult T-cell leukemia to p53-dependent senescence
|
| Tumor Cell Death | p21(Waf1) (P00039) | Inhibition of telomerase activity,progressive telomere shortening and increase p14(ARF) expression,elicit stabilization and reactivation of the tumor suppressor p53-dependent transcription, increased expression of the cyclin-dependent kinase inhibitor p21(Waf1) and accumulation of p27(kip1), thereby inducing cellular senescence and tumor cell death [ ADR Type 1 ] | Persistent inhibition of telomerase reprograms adult T-cell leukemia to p53-dependent senescence
|
| Tumor Suppression | wild-type p53 (P04637) | Those patients with a mutated p53 did not enter remission of tumor suppression following treatment with AZT and patients disease relapse was associated with the selection of a tumor clone carrying mutated inactive p53. [ ADR Type 2 ] | Persistent inhibition of telomerase reprograms adult T-cell leukemia to p53-dependent senescence
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