Differential effects of postconditioning on myocardial stunning and infarction: a study in conscious dogs and anesthetized rabbits

Postconditioning, i.e., brief intermittent episodes of myocardial ischemia-reperfusion performed at the onset of reperfusion, reduces infarct size after prolonged ischemia. Our goal was to determine whether postconditioning is protective against myocardial stunning. Accordingly, conscious chronically instrumented dogs (sonomicrometry, coronary balloon occluder) were subjected to a control sequence (10 min coronary artery occlusion, CAO, followed by coronary artery reperfusion, CAR) and a week apart to postconditioning with four cycles of brief CAR and CAO performed at completion of the 10 min CAO. Three postconditioning protocols were investigated, i.e., 15 s CAR/15 s CAO (n=5), 30 s CAR/30 s CAO (n=7), and 1 min CAR/1 min CAO (n=6). Left ventricular wall thickening was abolished during CAO and similarly reduced during subsequent stunning in control and postconditioning sequences (e.g., at 1 h CAR, 33+/-4 vs. 34+/-4%, 30+/-4 vs. 30+/-4%, and 33+/-4 vs. 32+/-4% for 15 s postconditioning, 30 s postconditioning, and 1 min postconditioning vs. corresponding control, respectively). We confirmed this result in anesthetized rabbits by demonstrating that shortening of left ventricular segment length was similarly depressed after 10 min CAO in control and postconditioning sequences (4 cycles of 30 s CAR/30 s CAO). In additional rabbits, the same postconditioning protocol significantly reduced infarct size after 30 min CAO and 3 h CAR (39+/-7%, n=6 vs. 56+/-4%, n=7 of the area at risk in postconditioning vs. control, respectively). Thus, contrasting to its beneficial effects on myocardial infarction, postconditioning does not protect against myocardial stunning in dogs and rabbits. Conversely, additional episodes of ischemia-reperfusion with postconditioning do not worsen myocardial stunning.     

Free radical reactions of a naturally occurring flavone baicalein and possible mechanisms towards its membrane protective properties

Baicalein (5, 6, 7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one), a naturally occurring flavone present in some of the medicinal plants is known for its potential therapeutic effects, such as cardioprotective, anticancer and anti-inflammatory properties. However, detailed role and mechanisms behind its protective properties against different generators for oxidative stress have not been examined. In the present study, we investigated the possible protective ability of baicalein against the membrane damage caused by reactive oxygen species (ROS) and reactive nitrogen species (RNS) and the mechanisms involved using pulse radiolysis technique. Baicalein offered efficient protection even at a concentration of 10 microM towards membrane damage caused by lipid peroxidation induced by the gamma-radiation, peroxyl radicals, ascorbate-Fe2+ and peroxynitrite in rat liver mitochondria and heart homogenate. To elucidate its reaction mechanisms with biologically relevant radicals, transient absorption spectroscopy employing pulse radiolysis technique was used. Baicalein showed fairly high rate constants (3.7 x 10(9), 1.3 x 10(9) and 8.0 x 10(8) dm3 mol(-1) s(-1) for hydroxyl, azidyl and alkylchloroperoxyl radicals, respectively), suggesting that baicalein can act as an effective scavenger of these radicals. In each case, the phenoxyl radical of baicalein was generated. Thus, it was evident that the phenolic moiety of baicalein was responsible for the free radical scavenging process. Baicalein also reacts with linoleic acid peroxyl radical (LOO*), indicating its ability to act as a chain breaking antioxidant. Peroxynitrite-mediated radicals were shown to be reactive towards baicalein and the bimolecular rate constants were 2.5 x 10(7) and 3 x 10(8) dm3 mol(-1) s(-1) for *NO2 and CO3*(-) radicals, respectively. In conclusion, our results revealed the potential of baicalein in protecting mitochondrial membrane against oxidative damage induced by the four different agents. We propose that the protective effect is mediated via scavenging of primary and secondary radicals generated during oxidative stress.     

Interaction of gibberellic and indole-3-acetic acid on root formation in pea (Pisum sativum L.) epicotyl cuttings

Indole-3-acetic acid (IAA) strongly enhanced rooting of etiolated pea epicotyl cuttings while gibberellic acid (GA₃) enhanced rooting only slightly. The promoting effects of the hormones appeared not until 14 d after the onset of treatment. When GA₃ and IAA were applied together, the initiation of rooting started already after 6 d after onset of treatment. It is suggested that gibberellin plays an important role, in combination with auxin, in the initiation of root formation in Pisum cuttings.Abbreviations IAA Indole-3-acetic acid - GA₃ Gibberellic acid     

Effects of cardiogenic edema fluid on ion and fluid transport in the adult lung

We have previously shown that cardiogenic pulmonary edema fluid (EF) increases Na(+) and fluid transport by fetal distal lung epithelia (FDLE) (Rafii B, Gillie DJ, Sulowski C, Hannam V, Cheung T, Otulakowski G, Barker PM and O'Brodovich H. J Physiol 544: 537-548, 2002). We now report the effect of EF on Na(+) and fluid transport by the adult lung. We first studied primary cultures of adult type II (ATII) epithelium and found that overnight exposure to EF increased Na(+) transport, and this effect was mainly due to factors other than catecholamines. Plasma did not stimulate Na(+) transport in ATII. Purification of EF demonstrated that at least some agent(s) responsible for the amiloride-insensitive component resided within the globulin fraction. ATII exposed to globulins demonstrated a conversion of amiloride-sensitive short-circuit current (I(sc)) to amiloride-insensitive I(sc) with no increase in total I(sc). Patch-clamp studies showed that ATII exposed to EF for 18 h had increased the number of highly selective Na(+) channels in their apical membrane. In situ acute exposure to EF increased the open probability of Na(+)-permeant ion channels in ATII within rat lung slices. EF did increase, by amiloride-sensitive pathways, the alveolar fluid clearance from the lungs of adult rats. We conclude that cardiogenic EF increases Na(+) transport by adult lung epithelia in primary cell culture, in situ and in vivo.     

Current Status of Our Understanding for Brain Integrated Functions and its Energetics

Neurochemical Research - Human/animal brain is a unique organ with substantially high metabolism but it contains no energy reserve that is the reason it requires continuous supply of O2 and energy...     

Cxcl12 evolution--subfunctionalization of a ligand through altered interaction with the chemokine receptor

The active migration of primordial germ cells (PGCs) from their site of specification towards their target is a valuable model for investigating directed cell migration within the complex environment of the developing embryo. In several vertebrates, PGC migration is guided by Cxcl12, a member of the chemokine superfamily. Interestingly, two distinct Cxcl12 paralogs are expressed in zebrafish embryos and contribute to the chemotattractive landscape. Although this offers versatility in the use of chemokine signals, it also requires a mechanism through which migrating cells prioritize the relevant cues that they encounter. Here, we show that PGCs respond preferentially to one of the paralogs and define the molecular basis for this biased behavior. We find that a single amino acid exchange switches the relative affinity of the Cxcl12 ligands for one of the duplicated Cxcr4 receptors, thereby determining the functional specialization of each chemokine that elicits a distinct function in a distinct process. This scenario represents an example of protein subfunctionalization--the specialization of two gene copies to perform complementary functions following gene duplication--which in this case is based on receptor-ligand interaction. Such specialization increases the complexity and flexibility of chemokine signaling in controlling concurrent developmental processes.