Autoschizis of T-cells is induced by the nutritional supplement, Cr(III)picolinate.
In recent times, Cr(III)(picolinate)(3) [Cr(III)(pic)(3)] a nutritional supplement, is gaining attention because of its clastogenic and mutagenic properties. Earlier studies of ours indicated that Cr(III)(pic)(3) is cytotoxic to lymphocytes with ROS and mitochondrial events playing a role in bringing about apoptosis. Now, we report that, autoschizis is induced in lymphocytes in a concentration and time dependent manner which is confirmed through TEM and SEM. Lymphocytes treated with concentrations of 100microM of Cr(III)(pic)(3) exhibit features such as cytoplasmic bleb, self excision of cytoplasm, cytoplasmic leakage and membrane bound bodies formed from the excised pieces apart from apoptosis and necrosis. Though autoschizis has been described in tumor cell lines treated with menadione and ascorbate, occurrence of this cell death in normal T-lymphocytes is reported here. The cellular events that accompany autoschizis are found to be increase in intracellular Reactive Oxygen Species (ROS) and cytoplasmic lactate dehydrogenase, loss of mitochondrial membrane potential (MMP) and depletion of ATP. Further, autoschizis is effected through increases in DNase I and DNase II activity with a concomitant decrease in caspase-3 activity which leads to a random cleavage of the DNA as demonstrated by a smear like pattern after electrophoresis on agarose gel.
Biochemistry Laboratory, Central Leather Research Institute, Adyar, Chennai 600 020, India.
Mahadevan
M
Jana
Rama
R
Rajaram
Anantanarayanan
A
Rajaram
D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000737:chemistry; D003850:Deoxyribonuclease I / Q000378:metabolism; D019587:Dietary Supplements / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004706:Endodeoxyribonucleases / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007502:Iron Chelating Agents / Q000633:toxicity*; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D010848:Picolinic Acids / Q000633:toxicity*
D007502:Iron Chelating Agents; D010848:Picolinic Acids; D004247:DNA; D004706:Endodeoxyribonucleases; D003850:Deoxyribonuclease I; C019329:deoxyribonuclease II; D053148:Caspase 3; C030614:picolinic acid