Deficiency in Methionine, Tryptophan, Isoleucine, or Choline Induces Apoptosis in Cultured Cells

Abstract

Cells in culture die by apoptosis when deprived of the essential nutrient choline. We now report that cells (both proliferating PC12 cells and postmitotic neurons isolated from fetal rat brains) undergo apoptosis when deprived of other individual essential nutrients (methionine, tryptophan or isoleucine). In PC12 cells, deficiencies of each nutrient independently led to ceramide accumulation and to caspase activation, both recognized signals of several apoptotic pathways. A similar profile of caspases was activated in PC12 cells deprived of choline, methionine, tryptophan or isoleucine. More than one caspase was involved and these caspases appeared to transmit parallel signals for apoptosis induction because only broad-spectrum caspase inhibitors, but not inhibitors for specific individual caspases inhibited apoptosis in choline- or methionine-deprived cells. The induction of these caspase-dependent apoptosis pathways likely did not involve the same upstream signals. Choline deficiency perturbed choline metabolism but did not affect protein synthesis, whereas amino acid deficiencies inhibited protein synthesis but did not perturb choline metabolism. In addition, a subclone of PC12 cells that was resistant to choline deficiency-induced apoptosis was not resistant to tryptophan deficiency-induced apoptosis. These observations suggest that deficiency of each studied nutrient activates different pathways for signaling apoptosis that ultimately converge on a common execution pathway.

Pathology of spleen in chickens fed on a diet deficient in methionine

“…The mechanisms of apoptosis are associated with accumulation of the ceramide and activation of caspase. It is reported that Met deficiency could activate one or more pathways for initiating apoptosis that ultimately converge on a common execution pathway [13]. According to the results in the present study, Met deficiency-induced apoptosis was associated with following factors: 1) The mitochondria damage.…”

“…Thus, Met deficiency can potentially interfere with any or all of the known mechanisms of worm expulsion whether antibody production and cell-mediated immunity, or mucosal mast cells are interfered with by a number of metabolic pathways [2]. And it is report that cells (both proliferating PC12 cells and postmitotic neurons isolated from fetal rat brains) undergo apoptosis when deprived of other individual essential nutrients (such as methionine) [13]. However, Met is the most toxic of the amino acids in rats, and an excess of a single amino acid often results in an imbalance [14,15].…”

PKCδ Is Activated in a Dietary Model of Steatohepatitis and Regulates Endoplasmic Reticulum Stress and Cell Death

“…It has been shown in long term (24 -72 h) culture with medium deficient in choline or methonine that protein and phospholipid synthesis are reduced (17,18). Long term culture with medium deficient in choline or methonine also results in programmed cell death (17,18), suggesting that depletion of intracellular pools of methyl group donors and choline moieties is detrimental for long term cell survival.…”

Biotin deficiency decreases life span and fertility but increases stress resistance in Drosophila melanogaster

“…Nutrient deficiency triggers cell stress [24][25][26]. Eukaryotic cells respond to stress caused by biotin deficiency with increased nuclear translocation of NF-κB (Rodriguez-Melendez R, Schwab LD, Zempleni J, submitted for publication), mediating expression of antiapoptotic genes such as Bfl-1/A1, Bcl-XL, and Nr13 [27,28].…”