We have examined whether 1) fatty acid (FA) uptake, 2) FA transporter expression, and 3) FA metabolism are increased when the oxidative capacity of skeletal muscle is increased. The oxidative capacities of red and white tibialis anterior and extensor digitorum longus muscles were increased via chronic stimulation (10 Hz, 24 h/day for 7 days). The contralateral muscles served as controls. After 7 days of increased muscle activity 1) palmitate uptake by giant sarcolemmal vesicles was increased twofold ( P < 0.05), 2) the expression of FA translocase (FAT)/CD36 was increased at both the mRNA (3.2- to 10-fold) and protein (3.4-fold) levels, and 3) palmitate oxidation and esterification into triacylglycerols and phospholipids were increased 1.5-, 2.7-, and 1.7-fold, respectively ( P < 0.05). These data show that when the oxidative capacity of muscle is increased, there is a parallel increase in the rate of FA transport and FA transporters at the sarcolemmal membrane, which is associated with the enhanced expression of the membrane transporter FAT/CD36.

The Proviral Integration site for Moloney murine leukemia virus (PIM) kinases is serine/threonine kinases that promote growth and survival in multiple cell types, implicated in the pathogenesis of various diseases. Over expression of Pim-1 experimentally leads to tumor formation in mice, whereas there is no observable phenotype concerning the complete knockout of the protein. When it is over expressed it may lead to cancer development by three major ways; by inhibiting apoptosis, by promoting cell proliferation and also through promoting genomic instability. Expression in normal tissues is nearly undetectable. Recent improvements in the development of novel inhibitors of PIMs have been reviewed. Significant progress in the design of PIMs inhibitors, in which it displays selectivity versus other kinases, has been achieved within the last years. However, the development of isoform-selective PIM inhibitors is still an open task. As Pim-1 possesses oncogenic functions and is over expressed in various kinds of cancer diseases, its inhibition provides a new option in cancer therapy. A PubMed literature search was performed to review the currently available data on Pim-1 expression, regulation, and targets; its implication in different types of cancer and its impact on prognosis is described. Consequently, designing new inhibitors of PIMs is now a very active area of research in academic and industrial laboratories.

In mammalian cells, membrane uptake of longchain fatty acids is mediated by two separate components; a passive component that is a linear function of the concentration of free fatty acid in the extracellular medium and a saturable component that exhibits the characteristics of a protein-facilitated process. This review summarizes the body of work that has accumulated related to the mechanism of fatty acid transport. Evidence in support of a facilitated uptake process is presented with relation to the different cell types or membrane systems where it was collected. The evidence includes saturation kinetics, competition between different substrates, and sensitivity to a variety of inhibitors. Recent knowledge related to membrane proteins thought to be implicated in the uptake process is reviewed. Factors that may modulate uptake or alter the relative contribution of passive versus facilitated components are briefly discussed. These include the molar ratio of fatty acid to its physiological carrier, plasma albumin and the metabolic or hormonal milieu.-Abumrad, N., C. Harmon, and A. Ibrahimi. Membrane transport of long-chain fatty acids: evidence for a facilitated process.