Glutamine and glutamate limit the shortening of action potential duration in anoxia-challenged rabbit hearts.

In clinical conditions, amino acid supplementation is applied to improve contractile function, minimize ischemia/reperfusion injury, and facilitate postoperative recovery. It has been shown that glutamine enhances myocardial ATP/APD (action potential duration) and glutathione/oxidized glutathione ratios, and can increase hexosamine biosynthesis pathway flux, which is believed to play a role in cardioprotection. Here, we studied the effect of glutamine and glutamate on electrical activity in Langendorff-perfused rabbit hearts.

Amino acids as metabolic substrates during cardiac ischemia.

The heart is well known as a metabolic omnivore in that it is capable of consuming fatty acids, glucose, ketone bodies, pyruvate, lactate, amino acids and even its own constituent proteins, in order of decreasing preference. The energy from these substrates supports not only mechanical contraction, but also the various transmembrane pumps and transporters required for ionic homeostasis, electrical activity, metabolism and catabolism. Cardiac ischemia - for example, due to compromise of the coronary vasculature or end-stage heart failure - will alter both electrical and metabolic activity.

Cell stiffness, contractile stress and the role of extracellular matrix.

Here we have assessed the effects of extracellular matrix (ECM) composition and rigidity on mechanical properties of the human airway smooth muscle (ASM) cell. Cell stiffness and contractile stress showed appreciable changes from the most relaxed state to the most contracted state: we refer to the maximal range of these changes as the cell contractile scope. The contractile scope was least when the cell was adherent upon collagen V, followed by collagen IV, laminin, and collagen I, and greatest for fibronectin.

RALBP1/RLIP76 mediates multidrug resistance.

RLIP76/RALBP1 is a multi-specific drug-transporter which can mediate drug-resistance in lung and other cancers, but its ability to mediate multidrug-resistance has not been previously demonstrated in hematological malignancy. Present studies in K562 human myelogenous leukemia show that RALBP1 overexpression confers broad resistance to multiple chemotherapy drugs including cisplatin, melphalan, doxorubicin, daunorubicin, vincristine, vinblastine, vinorelbine, and mitomycin-C. Conversely, inhibition of RALBP1 by polyclonal antibodies causes increased drug-accumulation and increased cytotoxicity.