Intracellular pH and the control of multidrug resistance.

Abstract

Many antcer drugs are dassi ased a either weak bases or molecules whose binding to cellular structures is pH dependent. Accumulation of these drugs within tumor cells should be affected by rane pH gradients. deed,

A novel energy dependent mechanism reducing daunorubicin accumulation in acute myeloid leukemia

“…This lation of weak bases such as daunorubicin may be influenced by the pH gradient across the surface membrane. 16,17 A relawas confirmed in the present series of experiments by demonstrating a lack of MRK-16 staining and low levels of CsAtive reduction in intracellular pH may cause decreased drug accumulation, because the equilibrium is shifted to the prodependent increases in daunorubicin accumulation in all five lines. Cells were treated with 2 mm KCN, 2 mm sodium azide, tonated form which diffuses much more slowly through lipid bilayers.…”

“…Alterations in intracellular pH have is clearly not essential for this since elevated P-gp or MRP levels are also seen in some untreated cancer patients, possbeen shown to affect cellular accumulation and subcellular distribution of weakly basic drugs such as daunorubicin. 16 ibly because the cancer is derived from a normal tissue that naturally expresses the resistance mechanism, or as a genetic However, no significant changes in intracellular pH were detected during 30 min exposure to 2 mm KCN. The most alteration occurring as part of the neoplatic process.…”

Alterations of intracellular pH homeostasis in apoptosis: origins and roles

“…antitumoral agents), one cannot preclude a role for intracellular acidification in the increased accumulation of the toxic drug. 53 …”

La biogenèse du VIH-1 dévoilée

“…Afin de nous assurer que ces virus étaient correctement libérés de la membrane plasmique, nous avons fusionné Gag à la protéine Phluorin, une variante de la GFP dont l'intensité d'émission est optimale à pH 7,5 et diminue avec l'acidification [11]. Une acidification rapide du cytoplasme des cellules peut être induite en exposant le milieu de culture à du CO 2 concentré à 100 % pendant 20 secondes [12]. En étudiant les conséquences de cette acidification sur la fluorescence de centaines de virus composés de milliers de copies de Gag-Phluorin, nous avons pu distinguer les virus qui étaient encore attachés à la cellule (ceux dont la fluorescence était très sensible aux changements de pH) de ceux qui avaient bourgeonné (ceux dont la fluorescence était peu sensible aux changements de pH du cytoplasme puisque séparés de la cellule) [9].…”