Effects of Trichlorotelluro-dypnones on Mitochondrial Bioenergetics and Their Relationship to the Reactivity with Protein Thiols

Author(s)

Yokomizo, Cesar H. ^[1] ; Pessoto, Felipe S. ^[2] ; Prieto, Tatiana ^[2] ; Cunha, Rodrigo L. O. R. ^[2] ; Nantes, Iseli L. ^[2]

Affiliation

^[1] Univ Fed Sao Paulo, Dept Biol Mol, Sao Paulo, SP - Brazil

^[2] Univ Fed ABC, Ctr Ciencias Nat & Humanas, Santo Andre, SP - Brazil

• Document type: Journal article
• Source: Chemical Research in Toxicology; v. 28, n. 6, p. 1167-1175, JUN 2015.
• Web of Science Citations: 1

Abstract

The effect of four trichlorotelluro-dypnones, named compounds 1, 2, 3, and 4, on the bioenergetics of isolated rat liver mitochondria (RLM) and cells was investigated. In a dose-dependent manner, the studied organotelluranes promoted Ca2+-dependent mitochondrial swelling inhibited by cyclosporine A and were associated with a decrease of the total mitochondrial protein thiol content. These effects characterize the opening of the classical mitochondrial permeability transition pore. Despite the reactivity with mitochondrial protein thiol groups, these compounds did not promote significant glutathione depletion. In the absence of Ca2+, the organotelluranes promoted mitochondrial loss of Delta Psi in RLM concomitant with respiratory control decrease due to an increase of the state 4 respiration rate. In these conditions, mitochondrial swelling was absent, and thiol content was higher than that in the presence of Ca2+. The differentiated effects observed in the presence and absence of Ca2+ are probably related to the effects of that ion on membrane structure, with repercussions for the exposure of specific reactive protein thiol groups. In smooth muscle cells, these compounds promoted the loss of mitochondrial Delta Psi and apoptosis. The loss of Delta Psi was not preceded by a decrease of cell viability that is consistent with mitochondria as the primary targets for the action of these organotelluranes. (AU)

• FAPESP's process: 12/07456-7 - Flow cytometry studies of cell death and protection promoted by porphyrinoid compounds, phenothiazines and Teluranes associated to nanostructures in a cell biology multiuser lab
• Grantee: Iseli Lourenço Nantes Cardoso
• Support Opportunities: Regular Research Grants
• FAPESP's process: 10/10349-2 - STUDY OF THE EFFECTS OF TELLURIUM COMPOUNDS AND THIOSEMICARBAZONES ON THIOL PROTEIN GROUPS
• Grantee: César Henrique Yokomizo
• Support Opportunities: Scholarships in Brazil - Doctorate