Premium
Protection from injury in Brown‐Norway rats may be due mitochondrial integrity following ischemia/reperfusion
Author(s) -
Basile David Patrick,
Camara Amadou,
Van Why Scott
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a336-d
Subject(s) - mitochondrion , ischemia , respiration , medicine , chemistry , cytoskeleton , endocrinology , atpase , adenosine triphosphate , biology , enzyme , biochemistry , anatomy , cell
We have shown that the Brown‐Norway rat (BN/Mcw) is markedly resistant to the development of ARF following I/R vs other rat strains. Furthermore, studies analyzing the cellular distribution of NaK‐ATPase suggest that BN rats maintain their cytoskeletal integrity immediately following I/R when compared to Sprague‐Dawley rats. Due to the relationship between ATP and cytoskeletal integrity, we investigated alterations in cellular energetics in BN rats in response to renal I/R injury. Renal cortical ATP content dropped to approximately 22 ± 6 % of control following 45 min of ischemia; levels recovered to 79 ± 7 % of control by 180 min reperfusion in SD rats. In contrast, ATP levels fell significantly less in the BN (37 ± 5 %) vs. control following ischemia and recovered to values significantly greater than control at 180 min 142 ±15%. State II and state III respiration were repressed following 1 hr of reperfusion using both complex I and complex II substrates; (e.g., state III inhibition of 59 ± 7% and 65±8 %, in response to pyruvate or succinate, respectively). In contrast, the inhibition in response to I/R in BN rat kidneys was significantly less than SD (23 ± 5% and 19 ± 6 %). In addition, transmission electron microscopy of cortical proximal tubules demonstrated prominent swelling in mitochondria of SD rat following I/R, while BN mitochondria were generally resistant to swelling. Taken together these data suggest that resistance to ARF in BN rats results from may attributable to mitochondrial integrity in the setting of I/R.