Oxidative Stress as Regulatory Factor for Fatty-Acid-Induced Uncoupling Involving Liver Mitochondrial ADP/ATP and Aspartate/Glutamate Antiporters of Old Rats

---

V. N. Samartsev^* and O. V. Kozhina

Mari State University, pl. Lenina 1, 424001 Yoshkar-Ola, Russia; fax: (8362) 56-5781; E-mail: samvic56@mail.ru

^* To whom correspondence should be addressed.

Received October 26, 2007; Revision received January 28, 2008

---

Palmitate-induced uncoupling, which involves ADP/ATP and aspartate/glutamate antiporters, has been studied in liver mitochondria of old rats (22-26 months) under conditions of lipid peroxidation and inhibition of oxidative stress by antioxidants--thiourea, Trolox, and ionol. It has been shown that in liver mitochondria of old rats in the absence of antioxidants and under conditions of overproduction of conjugated dienes, the protonophoric uncoupling activity of palmitate is not suppressed by either carboxyatractylate or aspartate used separately. However, the combination of carboxyatractylate and aspartate decreased uncoupling activity of palmitate by 81%. In this case, palmitate-induced uncoupling is limited by a stage insensitive to both carboxyatractylate and aspartate. In the presence of antioxidants, the palmitate-induced protonophoric uncoupling activity is suppressed by either carboxyatractylate or aspartate used separately. Under these conditions, palmitate-induced uncoupling is limited by a stage sensitive to carboxyatractylate (ADP/ATP antiporter) or aspartate (aspartate/glutamate antiporter). In the absence of antioxidants, the uncoupling activity of palmitate is not suppressed by ADP either in the absence or in the presence of aspartate. However, in the presence of thiourea, Trolox, or ionol ADP decreased the uncoupling activity of palmitate by 38%. It is concluded that in liver mitochondria of old rats the development of oxidative stress in the presence of physiological substrates of ADP/ATP and aspartate/glutamate antiporters (ADP and aspartate) results in an increase of the protonophoric uncoupling activity of palmitate.

---

KEY WORDS: liver mitochondria, aging, oxidative stress, reactive oxygen species, fatty acids, uncoupling, ADP/ATP antiporter, aspartate/glutamate antiporter

DOI: 10.1134/S0006297908070067

---