Apoptosis is induced by choline deficiency in fetal brain and in PC12 cells

Choline kinase inhibition induces the increase in ceramides resulting in a highly specific and selective cytotoxic antitumoral strategy as a potential mechanism of action

“…Thus, hexadecylphosphocholine (HePC), an inhibitor of CT, leads to a decrease not only in PC but also in SM, and the accumulation of ceramides (Sillence and Allan, 1998;Wieder et al, 1998), resulting in an atypical apoptosis (Cui and Houweling, 2002). The same effect can be generated by choline deprivation in the diet, the primary substrate for the Kennedy pathway (Holmes-McNary et al, 1997). In some cellular systems, such as PC12 cells, choline depletion induced apoptosis associated with a 50% reduction of PC content, but also …”

Opposing Regulation of Choline Deficiency-induced Apoptosis by p53 and Nuclear Factor κB

“…Cell Culture-PC12 cells were cultured as previously described (15). Briefly, cells were plated at a density of 2 ϫ 105 cells/plate in Dulbecco's modified Eagle's medium/F12 choline-free media (American Biogenics) supplemented with 10% fetal bovine serum, 5% horse serum, and 1% penicillin-streptomycin and maintained at 37°C in a 5% humidified incubator.…”

“…Briefly, cells were plated at a density of 2 ϫ 105 cells/plate in Dulbecco's modified Eagle's medium/F12 choline-free media (American Biogenics) supplemented with 10% fetal bovine serum, 5% horse serum, and 1% penicillin-streptomycin and maintained at 37°C in a 5% humidified incubator. For the following experiments, cells at 70% confluency were maintained in defined Dulbecco's modified Eagle's medium/F12 serumfree media as previously indicated (15). A parallel group of cells grown under the same conditions were exposed to either 0 rads (Sham) or 500 rads ␥ irradiation (␥-IRR) (100 rads ϭ 1 Gy).…”

“…Other pathophysiologic features associated with CD include caspase activation with diminished membrane phospholipids (8), induction of cyclooxygenase 2 (Cox-2) (9), elevated serum TNF-␣ (10), increased capability to transform rat hepatocytes (11), increased protein kinase C activity (12), enhanced induction of hepatocellular carcinoma in animals (13), and increased oxidative DNA damage (14). More recently, we have shown that CD can inhibit cell proliferation and can induce apoptosis in vivo and in vitro (15,16). Although CD is associated with many pathological effects, the molecular mechanism(s) by which CD exerts these effects…”

Maternal dietary choline availability alters the balance of netrin-1 and DCC neuronal migration proteins in fetal mouse brain hippocampus

“…We previously showed that, depending on the availability of maternal dietary choline, precursor cells in ventricular zone undergo proliferation and commit to differentiate into neuronal cell types (e.g., calretinin-containing cells) [8] known to regulate memory, or undergo apoptosis. We previously described how choline availability affects pro-apoptotic signal transduction in neuronal-type cells [18,28] and hepatocytes [1,4,6,7,9]. We are beginning to understand how maternal dietary choline availability during pregnancy affects not only the generation, but also the targeted migration of precursor neuronal-type cells in the fetal hippocampus [2,3,14].…”