| Full text | |
| Author(s): |
Genaro-Mattos, Thiago C.
[1]
;
Queiroz, Raphael F.
[1, 2]
;
Cunha, Daniela
[1]
;
Appolinario, Patricia P.
[1]
;
Di Mascio, Paolo
[1]
;
Nantes, Iseli L.
[3]
;
Augusto, Ohara
[1]
;
Miyamoto, Sayuri
[1]
Total Authors: 8
|
| Affiliation: | [1] Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-05508000 Sao Paulo, SP - Brazil
[2] Univ Estadual Sudoeste Bahia, Dept Quim & Exatas, BR-45200000 Jequie, BA - Brazil
[3] Univ Fed ABC, Ctr Ciencias Nat & Humanas, BR-09210580 Santo Andre, SP - Brazil
Total Affiliations: 3
|
| Document type: | Journal article |
| Source: | BIOCHEMISTRY; v. 54, n. 18, p. 2841-2850, MAY 12 2015. |
| Web of Science Citations: | 6 |
| Abstract | |
Lipid peroxidation is a well-known process that has been implicated in many diseases. Recent evidence has shown that mitochondrial cholesterol levels are increased under specific conditions, Making it an important target for peroxidation inside the mitochondria. Cholesterol peroxidation generates, as primary products, several hydroperoxides (ChOOH), which can react with transition metals and metalloproteins. In this sense, cytochrome c (CYTC), a heme protein largely found in the mitochondria, becomes a candidate to react with ChOOH. Using CYTC associated with SDS micelles to mimic mitochondrial conditions, we show that ChOOH induces dose-dependent CYTC Soret hand bleaching, indicating that it is using ChOOH as a substrate. This reaction leads to protein oligomerization, suggesting the formation of a protein radical that, subsequently, recombines, giving dimers, trimers, and tetramers. EPR. experiments confirmed the production of carbon-centered radicals from both protein and lipid in the presence of ChOOH. Similar results were obtained with linoleic acid hydroperoxides (LAOOH). In addition, replacing SDS micelles by cardiolipin-containing liposomes as the mitochondrial mimetic led to Similar results with either ChOOH or LAO OH. Importantly, kinetic experiments show that CYTC bleaching is faster with ChOOH than with H2O2, suggesting that these hydroperoxides could be relevant substrates for CYTC peroxidase-like activity in biological media. Altogether, these results show that CYTC induces homolytic cleavage of lipid-derived hydroperoxides, producing lipid and protein radicals. (AU) | |
| FAPESP's process: | 08/57721-3 - Redoxome |
| Grantee: | Ohara Augusto |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 12/12663-1 - Singlet molecular oxygen and peroxides in chemical biology |
| Grantee: | Paolo Di Mascio |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 13/07937-8 - Redoxome - Redox Processes in Biomedicine |
| Grantee: | Ohara Augusto |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |