Zinc protects human peripheral blood lymphocytes from Cr(III)(phenanthroline){sub 3}-induced apoptosis

Journal Article · Mon Mar 15 00:00:00 EDT 2010 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2009.12.018· OSTI ID:21344899

Sankaramanivel, Sundararaj ^[1]; Rajaram, Anantanarayanan ^[2]; Rajaram, Rama ^[1]

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1. Biochemistry Laboratory, Central Leather Research Institute, Adyar, Chennai-600 020 (India)
2. Biophysics Laboratory, Central Leather Research Institute, Adyar, Chennai (India)

We have studied the effect of Cr(III)(phen){sub 3} [(tris(1,10-phenanthroline) chromium(III) chloride)] on lymphocytes in order to find out if metallothioneins (MTs) are produced in the process. We also investigated whether zinc pretreatment is able to protect cells from apoptosis reported to occur for this compound. Our results indicate that MT synthesis is induced by Cr(III)(phen){sub 3}, and it has been identified as the MT-3 isoform through RT-PCR which has not been reported earlier. By zinc pretreatment, this apoptosis is reversed as inferred from cytotoxicity studies, Annexin-V/PI staining, ethidium bromide/acridine orange staining and DNA fragmentation pattern and ultrastructural investigations using TEM and SEM. The zinc pretreatment reduces the amount of ROS produced by Cr(III)(phen){sub 3} . The MT-1a and 1b synthesized by zinc (also evidenced through RT-PCR experiments) is possibly able to scavenge ROS which is one of the early signaling molecules that lead to apoptosis. Zinc pretreatment also reverses the changes in downstream signaling events such as mitochondrial membrane potential, ATP levels and the activation of caspase-3. This is the first report on the induction of MT-3 in lymphocytes due to a metal stress or any other stimuli. Even though MT-3 is synthesized here, apoptosis still occurs due to ROS production on Cr(III)(phen){sub 3} exposure when the cells have not been primed with zinc.

• OSTI ID: 21344899
• Journal Information: Toxicology and Applied Pharmacology, Vol. 243, Issue 3; Other Information: DOI: 10.1016/j.taap.2009.12.018; PII: S0041-008X(09)00525-0; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ACRIDINE ORANGE
APOPTOSIS
BROMIDES
CHLORIDES
CHROMIUM COMPLEXES
LYMPHOCYTES
MEMBRANES
MEN
METALLOTHIONEIN
MITOCHONDRIA
PHENANTHROLINES
SCANNING ELECTRON MICROSCOPY
STIMULI
STRESSES
TOXICITY
TRANSMISSION ELECTRON MICROSCOPY
ZINC
ACRIDINES
AMINES
ANIMAL CELLS
ANIMALS
AROMATICS
AZAARENES
AZINES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
BROMINE COMPOUNDS
CELL CONSTITUENTS
CHLORINE COMPOUNDS
COMPLEXES
CONNECTIVE TISSUE CELLS
DYES
ELECTRON MICROSCOPY
ELEMENTS
HALIDES
HALOGEN COMPOUNDS
HETEROCYCLIC COMPOUNDS
LEUKOCYTES
MALES
MAMMALS
MAN
MATERIALS
METALLOPROTEINS
METALS
MICROSCOPY
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PRIMATES
PROTEINS
PYRIDINES
SOMATIC CELLS
TRANSITION ELEMENT COMPLEXES
VERTEBRATES