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Phosphatidylinositol 3-kinase is involved in the protection of primary cultured human erythroid precursor cells from apoptosis

, : Phosphatidylinositol 3-kinase is involved in the protection of primary cultured human erythroid precursor cells from apoptosis. Blood 94(5): 1568-1577

Little is known about the physiologic role of phosphatidylinositol 3-kinase (PI-3K) in the development of erythrocytes. Previous studies have shown that the effects of the PI-3K inhibitor wortmannin on erythropoietin (EPO)-dependent cell lines differed depending on the cell type used. Wortmannin inhibited EPO-induced differentiation of some cell lines without affecting their proliferation; however, the EPO-induced proliferation of other cell lines was inhibited by wortmannin. In neither case were signs of apoptosis observed. We have previously reported that signaling in highly purified human colony forming units-erythroid (CFU-E), generated in vitro from CD34(+) cells, differed from that in EPO-dependent cell lines. In the current study, we examined the effects of a more specific PI-3K inhibitor (LY294002) on human CFU-E. We found that LY294002 dose-dependently inhibits the proliferation of erythroid progenitor cells with a half-maximal effect at 10 micromol/L LY294002. LY294002 at similar concentrations also induces apoptosis of these cells, as evidenced by the appearance of annexin V-binding cells and DNA fragmentation. The steady-state phosphorylation of AKT at Ser-473 that occurs as a result of PI-3K activation was also inhibited by LY294002 at similar concentrations, suggesting that the effects of LY294002 are specific. Interestingly, the acceleration of apoptosis by LY294002 was observed in the presence or absence of EPO. Further, deprivation of EPO resulted in accelerated apoptosis irrespective of the presence of LY294002. Our study confirms and extends the finding that signaling in human primary cultured erythroid cells is significantly different from that in EPO-dependent cell lines. These data suggest that PI-3K has an antiapoptotic role in erythroid progenitor cells. In addition, 2 different pathways for the protection of primary erythroid cells from apoptosis likely exist: 1 independent of EPO that is LY294002-sensitive and one that is EPO-dependent and at least partly insensitive to LY294002.


PMID: 10477682

Other references

Gleichauf, R., 1973: Age-related changes in semen volume and sperm concentration in Leghorn cocks of different lines. Investigations on the semen volume and sperm concentration of 35 Leghorn cocks from 3 lines at 7-10 and 12-13 mth of age revealed that both these characters decreased with increasing age. There were high correlations between each cock's perfo...

Diker, E.; Canbay, A.; Celebi, O.Ozcan.; Sahin, D.; Uçar, Oül.; Aydoğdu, S., 2008: Ablation of right ventricular outflow tract tachycardias under guidance of noncontact mapping system. We evaluated the efficiency of noncontact mapping, a new mapping technique, for the catheter ablation of right ventricular outflow tract tachycardias. The study included 13 symptomatic patients (4 males, 9 females; mean age 39+/-15 years) with a s...

Solanto, M.V.; Marks, D.J.; Mitchell, K.J.; Wasserstein, J.; Kofman, M.D., 2007: Development of a new psychosocial treatment for adult ADHD. The purpose of this study was to assess the effectiveness of a new manualized group Meta-Cognitive Therapy (MCT) for adults with ADHD that extends the principles and practices of cognitive-behavioral therapy to the development of executive self-ma...

Lazarus, C.L.; Husaini, H.; Jacobson, A.S.; Mojica, J.K.; Buchbinder, D.; Okay, D.; Urken, M.L., 2016: Development of a new lingual range-of-motion assessment scale: normative data in surgically treated oral cancer patients. Surgical resection in oral cancer patients can result in altered speech, swallowing, and patient perception of quality of life (QOL). Oral surgery can result in reduced lingual range of motion (ROM). However, few studies have quantified the degree...

Bolgert, M.; Dufourmentel, C.; L.S.Urd, M., 1951: Surgical excision and graft of a fibroblastic sarcoma which developed on a former radiodermatitis; confirmed cure after eleven months. Bulletins et Memoires de la Societe Medicale des Hopitaux de Paris 67(31-32): 1359-1360

Fromm, C.; Bauswein, E., 1994: Distributed processing of movement dynamics and kinematics in the three motor cortical areas of the rhesus monkey. Albowitz, B [Editor], Albus, K [Editor], Kuhnt, U [Editor], Nothdurft, H -Ch [Editor], Wahle, P [Editor] Experimental Brain Research Series; Structural and functional organization of the neocortex 415-422

Nelson, E., 1959: Cerebral localization. South Dakota Journal of Medicine and Pharmacy 12(1): 7-12

Kuhn, H.F.; Friebel, H., 1960: On the arrangement of the cough impulse into the respiratory rhythm. Medicina Experimentalis 3: 329-335

Kaneko, K.; Shirai, Y.; Wakai, T.; Hasegawa, G.; Kaneko, I.; Hatakeyama, K., 2003: Hemangiopericytoma arising in the greater omentum: report of a case. Although hemangiopericytoma may arise in any anatomic site, it rarely develops in the greater omentum. To our knowledge, only ten cases have been reported to date in the English-language literature. We report herein an additional case of hemangiop...

Soderberg, L.S.F.; Ponnappan, U., 2002: The abused inhalant, isobutyl nitrite, is cytotoxic by means other than peroxynitrite formation. Drug & Alcohol Dependence 66(Supplement 1): S168, 1 May