title: Bis(N,N-dimethylhydroxamido)hydroxooxovanadate inhibition of protein tyrosine phosphatase activity in intact cells: comparison with vanadate.
abstract: We have shown previously that bis(N,N-dimethylhydroxamido)hydroxooxovanadate (DMHV) is an excellent reversible inhibitor of protein tyrosine phosphatase (PTP) in vitro. DMHV does not carry a charge under physiological pH conditions and is anticipated to permeate cell membranes more easily than vanadate. In the present study, the efficacy of DMHV as a PTP inhibitor in intact cells was compared with that of vanadate by measuring phosphotyrosine levels in various cells treated with these compounds. DMHV was more effective in increasing both the phosphotyrosine levels of various proteins in 3T3L1 fibroblasts and the level of insulin-receptor phosphorylation in CHO cells overexpressing the human insulin receptor. DMHV was about 10- to 20-fold more effective than vanadate in increasing glucose transport and glycogen synthesis in 3T3L1 adipocytes. DMHV, unlike vanadate, also inhibited PTP in Jurkat cells. The implications of these observations are discussed.
authors.affiliation: Department of Biochemistry and Molecular Biology, Merck Frosst Center for Therapeutic Research, Pointe-Claire-Dorval, Quebec, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Cuncic
authors.forename: S
authors.initials: S
authors.lastname: Desmarais
authors.forename: N
authors.initials: N
authors.lastname: Detich
authors.forename: A S
authors.initials: AS
authors.lastname: Tracey
authors.forename: M J
authors.initials: MJ
authors.lastname: Gresser
authors.forename: C
authors.initials: C
authors.lastname: Ramachandran
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D016466:CHO Cells; D006224:Cricetinae; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000096:biosynthesis; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D019000:Phosphotyrosine / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D014638:Vanadates / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; C402001:bis(N,N-dimethylhydroxamido)hydroxooxovanadate; D019000:Phosphotyrosine; D014638:Vanadates; D006003:Glycogen; D011972:Receptor, Insulin; D017027:Protein Tyrosine Phosphatases; D005947:Glucose