Effect of phloretin on the permeability of thin lipid membranes.

Abstract

A B S T R A C T Phloretin dramatically increases cation conductances and decreasesanion conductances of membranes treated with ion carriers (nonactin, valinomycin, carbonyl-cyanide-m-chiorophenylhydrazone [CCCP], and Hg(CnFs)2) or lipophilic ions (tetraphenylarsonium [TPhAs +] and tetraphenylborate [TPhB-]). For example, on phosphatidylethanolamine membranes, 10 -4 M phloretin increases K+-nonactin and TPhAs + conductances and decreases CCCP-and TPhBconductances 10a-fold; on lecithin:cholesterol membranes, it increases K+-nonactin conductance 1on-fold and decreases CCCP-conductance 10n-fold. Similar effects are obtained with p-and m-nitrophenol at 10 -2 M. These effects are produced by the un-ionized form of phioretin and the nitrophenols. We believe that phloretin, which possesses a large dipole moment, adsorbs and orients at the membrane surface to introduce a dipole potential of opposite polarity to the preexisting positive one, thus increasing the partition coefficient of cations into the membrane interior and decreasing the partition coefficient of anions. (Phloretin may also increase the fluidity of cholesterol-containing membranes; this is manifested by its two-to threefold increase in nonelectrolyte permeability and its asymmetrical effect on cation and anion conductances in cholesterol-containing membranes.) It is possible that phloretin's inhibition of chloride, urea, and glucose transport in biological membranes results from the effects of these intense interfacial dipole fields on the translocator(s) of these molecules.

Characterization of Phloretin-Sensitive Urea Export from the Perfused Rat Liver

“…With these compounds, urea effects comparable to those observed in presence of phloretin, although to a much lesser extent, were measured. These findings are in good agreement with the observation by other investigators that hydroxylated phenol compounds affect membrane permeability in a similar fashion to phloretin, although much higher concentrations are required and the effects are less pronounced than those with phloretin, at least in artificial bilayers or in erythrocytes (Andersen et al, 1976;Deuticke et a/., 1991).…”

Accumulation of a nod gene inducer, the flavonoid naringenin, in the cytoplasmic membrane of Rhizobium leguminosarum biovar viciae is caused by the pH-dependent hydrophobicity of naringenin

“…4), presumably because at high pH the ionizable hydroxyl groups at positions C-7 and C-4' of naringenin become negatively charged. A similar pH-dependent binding has been reported for the structurally related flavonoid phloretin to human erythrocytes (15) and black lipid membranes (1). Uncharged phloretin is able to increase the permeability of lipid membranes for ions, and it has been proposed that it interacts with the phospholipid bilayer due to its bipolar properties (1).…”

A haploid genetic screen identifies the major facilitator domain containing 2A (MFSD2A) transporter as a key mediator in the response to tunicamycin

“…CPZ inhibits various ATPases, including Na + -K + -ATPase, thereby reducing both the electrochemical sodium gradient and sodium-dependent solute transport (52,53). Phloretin impinges on nonelectrolyte and ion membrane transport and more specifically, inhibits sugar, urea, and chloride transport (54). Interestingly, simultaneous treatment of MFSD2A-overexpressing cells with TM and CPZ or Phloretin largely negated GRP78 and CHOP induction observed with TM treatment alone (Fig.…”