Irving Boime

The role of fatty acids in mitochondrial changes during liver ischemia

Abstract Exposure of rat liver to periods of ischemia results in a progressive increase in mitochondrial free fatty acids (FFA). The levels increase some 6–7-fold when the liver has been ischemic either for 2 hr at 38 ° or 13 hr at 24 °. A decline in respiratory control (rate of O2 uptake with ADP/rate of O2 uptake without ADP) parallels the rise in FFA at both temperatures. Significant depression of respiratory control is observed when comparable amounts of FFA are added to normal mitochondria. Bovine serum albumin (BSA), which restores respiratory control to a considerable degree and enhances the stability of mitochondria isolated from ischemic tissue, reduces the FFA levels about 70%. Despite the presence of BSA during isolation and testing of the mitochondria, there is still a gradual decline in the respiratory control ratio over a period of ischemia lasting several hours, primarily because of a diminution in the state 3 rate of respiration. The levels of mitochondrial phosphatidyl ethanolamine decreased somewhat, but the percentage change was small. Phosphatidyl choline remained essentially unchanged. A more significant decrease in cardiolipin was observed. Part of this change must be ascribed to dilution of the mitochondria by increased microsomal contamination. The data suggest that mitochondrial changes during ischemia involve (a) a BSA-reversible phase produced by FFA released by lipolysis, and (b) a further change, not reversed by BSA, which may be due to loss of essential mitochondrial lipid like cardiolipin, the presence of lysophosphatides, or proteolysis. Morphological changes in mitochondria in liver sections are consistent with these interpretations.

Messenger RNA Dependent Synthesis of a Protein Containing Relaxin Related Sequences

Serum relaxin levels in pregnant rats, sows, and guinea pigs are very low during most of gestation (Sherwood et al. 1975); mean relaxin concentrations in the sow range between 0.1 and 2.0 ng/ml throughout the first 100 days of pregnancy. During this period small electron dense cytoplasmic granules begin to appear in luteal cells. This granule population continued to increase in late gestation, reaching a maximum several days before parturition. About 24–48 hours before delivery a rapid disintegration of the cytoplasmic granules occurs. Serum levels of relaxin rise rapidly and then drop precipitously during parturition and lactation (Belt et al.3 1971). Studies in rat ovarian homogenates also suggest a steady, gradual rise in relaxin production throughout pregnancy (Sherwood and Crnekovic, 1979). The stimuli for the initial production of the hormone, the factors controlling its secretion and storage during pregnancy, and the reasons for its explosive release at term remain obscure. Relaxin has traditionally been assigned to the class of pregnancy-related hormones, but at least one study suggests that in humans the protein is also present in non-pregnant sera (Bryant-Greenwood et al.3 1977).