Linked Life Data

10727263

Source:http://linkedlifedata.com/resource/pubmed/id/10727263

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2000-5-9
pubmed:abstractText
We previously demonstrated that bis-cyclopentadienyl (Cp) complexes of vanadium(IV) (vanadocenes) are potent spermicidal and apoptosis-inducing agents. To gain further insight into the structure-function relationships controlling these two properties of vanadocenes, we have synthesized analogues in which the bis-Cp rings were substituted with one or five electron-donating methyl groups. The three complexes included vanadocene dichloride (VDC), bis(methylcyclopentadienyl) vanadium dichloride (VMDC), and bis(pentamethylcyclopentadienyl) vanadium dichloride (VPMDC). The concentration-dependent effect of these vanadocenes on sperm-immobilizing activity (SIA), mitochondrial membrane potential (DeltaPsim), axonemal dynein ATPase activity, and tyrosine phosphorylation of global and axoneme-specific sperm proteins was assessed by computer-assisted sperm analysis, flow cytometry, colorimetry, and immunoblotting, respectively. Apoptosis-inducing ability was quantitated by the two-color flow cytometric terminal dideoxynucleotidyl transferase-based assay that labels 3'-hydroxyl ends of fragmented DNA. All three vanadocenes induced rapid sperm immobilization (T(1/2) < 15 sec). Substitution of the bis-Cp rings by five methyl groups augmented the SIA of VDC by 10-fold. The EC(50) values (50% inhibitory concentration) for VDC, VMDC, and VPMDC were 7.5 microM, 4.3 microM, and 0.7 microM, respectively. Whereas SIA of vanadocenes was apparent at low micromolar concentrations, the apoptosis-inducing property was evident only at higher micromolar concentrations. The concentrations of VDC, VMDC, and VPMDC required for 50% apoptosis were 49 microM, 67 microM, and 153 microM, and for 50% reduction in sperm DeltaPsim were 435 microM, 173 microM, and 124 microM, respectively. Spermicidal activity of vanadocenes was not dependent on the inhibition of ATPase or tyrosine phosphorylation of global and sperm axonemal proteins. Due to the ability of these vanadocene complexes to rapidly generate hydroxyl radicals in the presence of oxidant, our findings provide unprecedented evidence for a novel mechanism of action for spermicidal vanadocenes. The differential concentration-dependent spermicidal and apoptosis-inducing properties of vanadocenes gives them particular utility as a new class of vaginal contraceptives.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0006-3363
pubmed:author
pubmed:issnType
Print
pubmed:volume
62
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
939-49
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:10727263-Apoptosis, pubmed-meshheading:10727263-Biomechanics, pubmed-meshheading:10727263-Blotting, Western, pubmed-meshheading:10727263-Coloring Agents, pubmed-meshheading:10727263-DNA Fragmentation, pubmed-meshheading:10727263-Dyneins, pubmed-meshheading:10727263-Female, pubmed-meshheading:10727263-Flow Cytometry, pubmed-meshheading:10727263-Humans, pubmed-meshheading:10727263-In Situ Nick-End Labeling, pubmed-meshheading:10727263-Male, pubmed-meshheading:10727263-Membrane Potentials, pubmed-meshheading:10727263-Phosphates, pubmed-meshheading:10727263-Phosphotyrosine, pubmed-meshheading:10727263-Sperm Motility, pubmed-meshheading:10727263-Spermatocidal Agents, pubmed-meshheading:10727263-Spermatozoa, pubmed-meshheading:10727263-Structure-Activity Relationship, pubmed-meshheading:10727263-Tetrazolium Salts, pubmed-meshheading:10727263-Thiazoles, pubmed-meshheading:10727263-Vagina, pubmed-meshheading:10727263-Vanadium Compounds
pubmed:year
2000
pubmed:articleTitle
Studies in humans on the mechanism of potent spermicidal and apoptosis-inducing activities of vanadocene complexes.
pubmed:affiliation
Drug Discovery Program, Departments of Reproductive Biology and Biochemistry, Parker Hughes Institute, St. Paul, Minnesota 55113, USA. odcruz@ih.org
pubmed:publicationType
Journal Article, In Vitro