Inhibition of erythrocyte “apoptosis” by catecholamines

Abstract

Osmotic shock, oxidative stress and Cl- removal activate a non-selective Ca2+-permeable cation conductance in human erythrocytes. The entry of Ca2+ leads to activation of a scramblase with subsequent exposure of phosphatidylserine at the cell surface. Phosphatidylserine mediates binding to phosphatidylserine receptors on macrophages which engulf and degrade phosphatidylserine exposing cells. Moreover, phosphatidylserine exposure may lead to adherence of erythrocytes to the vascular wall. In the present study, we explored whether activation of the non-selective cation conductance and subsequent phosphatidylserine exposure might be influenced by catecholamines. Phosphatidylserine exposure has been determined by FITC-annexin V binding while cell volume was estimated from forward scatter in FACS analysis. Removal of Cl- enhanced annexin binding and decreased forward scatter, an effect significantly blunted by the beta agonist isoproterenol (IC50 approx. 1 microM). Fluo-3 fluorescence measurements revealed an increase of cytosolic Ca2+ activity following Cl- removal, an effect again significantly blunted by isoproterenol exposure (10 microM). Whole-cell patch-clamp experiments performed in Cl- free bath solution indeed disclosed a time-dependent inactivation of a non-selective cation conductance following isoproterenol exposure (10 microM). Phenylephrine (IC50<10 microM), dobutamine (IC50 approx. 1 microM) and dopamine (IC50 approx. 3 microM) similarly inhibited the effect of Cl- removal on annexin binding and forward scatter. In conclusion, several catecholamines inhibit the Cl- removal-activated Ca2+ entry into erythrocytes, thus preventing increase of cytosolic Ca2+ activity, subsequent cell shrinkage and activation of erythrocyte scramblase. The catecholamines thus counteract erythrocyte phosphatidylserine exposure and subsequent clearance of erythrocytes from circulating blood.

Erythrocyte programmed cell death

“…The catecholamines dopamine, isoproterenol and epinephrine have similarly been shown to inhibit the Ca 21 -permeable cation channels and thus again to counteract eryptosis (101). Accordingly, catecholamines reverse the toxicity of cyclophosphamide (102).…”

Effect of Anandamide on Erythrocyte Survival

“…Eryptosis is triggered by activation of Ca 2+ -permeable erythrocyte cation channels [30][31][32] -sensitive scrambling of the cell membrane [35] with phosphatidylserine exposure at the cell surface [30]. Eryptosis is further elicited by ceramide (acylsphingosine) [36].…”

Quantitative expression analysis and prognostic significance of L-DOPA decarboxylase in colorectal adenocarcinoma

“…L-DOPA decarboxylase is a PLP-dependent enzyme participating in the catecholamine biosynthesis pathway, responsible principally for the synthesis of the key neurotransmitters DA and 5-HT (Christenson et al, 1972). Biogenic amines are generally considered to participate in various processes, such as angiogenesis, cell proliferation, differentiation and apoptosis (Berry et al, 1996;Medina et al, 1999;Lang et al, 2005), which implies a potentially significant role of DDC in cancer pathobiology and progression. Interestingly enough, it has recently been shown that catecholamines, including DA itself, inhibit erythrocyte apoptosis by preventing scramblase activation and subsequent phosphatidylserine exposure on the cell membrane (Lang et al, 2005), which in turn triggers clearance of apoptotic cells by macrophages.…”