Hydrogen sulfide as an oxygen sensor in trout gill chemoreceptors

O2 chemoreceptors elicit cardiorespiratory reflexes in all vertebrates, but consensus on O2-sensing signal transduction mechanism(s) is lacking. We recently proposed that hydrogen sulfide (H2S) metabolism is involved in O2 sensing in vascular smooth muscle. Here, we examined the possibility that H2S is an O2 sensor in trout chemoreceptors where the first pair of gills is a primary site of aquatic O2 sensing and the homolog of the mammalian carotid body. Intrabuccal injection of H2S in unanesthetized trout produced a dose-dependent bradycardia and increased ventilatory frequency and amplitude similar to the hypoxic response. Removal of the first, but not second, pair of gills significantly inhibited H2S-mediated bradycardia, consistent with the loss of aquatic chemoreceptors. mRNA for H2S-synthesizing enzymes, cystathionine beta-synthase and cystathionine gamma-lyase, was present in branchial tissue. Homogenized gills produced H2S enzymatically, and H2S production was inhibited by O2, whereas mitochondrial H2S consumption was O2 dependent. Ambient hypoxia did not affect plasma H2S in unanesthetized trout, but produced a PO2-dependent increase in a sulfide moiety suggestive of increased H2S production. In isolated zebrafish neuroepithelial cells, the putative chemoreceptive cells of fish, both hypoxia and H2S, produced a similar approximately 10-mV depolarization. These studies are consistent with H2S involvement in O2 sensing/signal transduction pathway(s) in chemoreceptive cells, as previously demonstrated in vascular smooth muscle. This novel mechanism, whereby H2S concentration ([H2S]) is governed by the balance between constitutive production and oxidation, tightly couples tissue [H2S] to PO2 and may provide an exquisitely sensitive, yet simple, O2 sensor in a variety of tissues.     

Alterations in carbohydrate metabolism and its regulation in PPARalpha null mouse hearts

Although a shift from fatty acids (FAs) to carbohydrates (CHOs) is considered beneficial for the diseased heart, it is unclear why subjects with FA beta-oxidation defects are prone to cardiac decompensation under stress conditions. The present study investigated potential alterations in the myocardial utilization of CHOs for energy production and anaplerosis in 12-wk-old peroxisome proliferator-activating receptor-alpha (PPARalpha) null mice (a model of FA beta-oxidation defects). Carbon-13 methodology was used to assess substrate flux through energy-yielding pathways in hearts perfused ex vivo at two workloads with a physiological substrate mixture mimicking the fed state, and real-time RT-quantitative polymerase chain reaction was used to document the expression of selected metabolic genes. When compared with that from control C57BL/6 mice, isolated working hearts from PPARalpha null mice displayed an impaired capacity to withstand a rise in preload (mimicking an increased venous return as it occurs during exercise) as reflected by a 20% decline in the aortic flow rate. At the metabolic level, beyond the expected shift from FA (5-fold down) to CHO (1.5-fold up; P < 0.001) at both preloads, PPARalpha null hearts also displayed 1) a significantly greater contribution of exogenous lactate and glucose and/or glycogen (2-fold up) to endogenous pyruvate formation, whereas that of exogenous pyruvate remained unchanged and 2) marginal alterations in citric acid cycle-related parameters. The lactate production rate was the only measured parameter that was affected differently by preloads in control and PPARalpha null mouse hearts, suggesting a restricted reserve for the latter hearts to enhance glycolysis when the energy demand is increased. Alterations in the expression of some glycolysis-related genes suggest potential mechanisms involved in this defective CHO metabolism. Collectively, our data highlight the importance of metabolic alterations in CHO metabolism associated with FA oxidation defects as a factor that may predispose the heart to decompensation under stress conditions even in the fed state.     

Increased Dopaminergic Neuron Sensitivity to 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) in Transgenic Mice Expressing Mutant A53T α-Synuclein

Familial Parkinson’s disease (PD) has been linked to point mutations and duplication of the α-synuclein gene and mutant α-synuclein expression increases the vulnerability of neurons to exogenous insults. In this study, we analyzed the levels of dopamine and its metabolites in the olfactory bulb (OB), and nigrostriatal regions of transgenic mice expressing human, mutant A53T α-synuclein (α-syn tg) and their non-transgenic (ntg) littermates using a sub-toxic, moderate dose of MPTP to determine if mutant human α-synuclein sensitizes the central dopaminergic systems to oxidative stress. We observed that after a single, sub-lethal MPTP injection, dopamine levels were reduced in striatum and SN in both the α-syn tg and ntg mice. In the olfactory bulb, a region usually resistant to MPTP toxicity, levels were reduced only in the α-syn tg mice. In addition, we identified a significant increase in dopamine metabolism in the α-syn transgenic, but not ntg mice. Finally, MPTP treatment of α-syn tg mice was associated with a marked elevation in the oxidative product, 3-nitrotyrosine that co-migrated with α-synuclein. Cumulatively, the data support the hypothesis that mutant α-synuclein sensitizes dopaminergic neurons to neurotoxic insults and is associated with greater oxidative stress. The α-syn tg line is therefore useful to study the genetic and environmental inter-relationship in PD.     

Reshaping of sandstone surfaces by cryptoendolithic cyanobacteria: bioalkalization causes chemical weathering in arid landscapes

We report a novel weathering mechanism in South African sandstone formations, where cryptoendolithic cyanobacteria induce weathering by substrate alkalization during photosynthesis. As a result, the upper rock part is loosened and then eroded away by physical forces such as wind, water, trampling. This special type of ‘exfoliation’ is widely distributed and affects the geomorphology of whole sandstone mountain ranges and outcrops across several biomes. We show, that this weathering type is initiated by bioalkalization because of the photosynthesis of cryptoendolithic (i.e. those organisms living in small tight open spaces between the sand grains) cyanobacteria causing pH values high enough to enhance silica solution in the cryptoendolithic zone. As modern cyanobacteria are the initial photoautotrophic colonizers of bare rocks in arid and semiarid landscapes, it is possible that they may also have played a significant role in shaping sandstone landscapes in the geological past.     

Linear and threshold-dependent expression of secondary sexual traits in the same individual: insights from a horned beetle (Coleoptera: Scarabaeidae)

Elaborate horns or horn‐like structures in male scarab beetles commonly scale with body size either (a) in a linear fashion with horn size increasing relatively faster than body size or (b) in a threshold‐dependent, sigmoid fashion; that is, males smaller than a certain critical body size develop no or only rudimentary horns, whereas males larger than the threshold size express fully developed horns. The development of linear vs. sigmoid scaling relationships is thought to require fundamentally different regulatory mechanisms. Here we show that such disparate regulatory mechanisms may co‐occur in the same individual. Large males of the south‐east Asian Onthophagus (Proagoderus) watanabei (Ochi & Kon) (Scarabaeidae, Onthophagini) develop a pair of long, curved head horns as well as a single thoracic horn. We show that unlike paired head horns in a large number of Onthophagus species, in O. watanabei the relationship between head horns and body size is best explained by a linear model. Large males develop disproportionately longer horns than small males, but the difference in relative horn sizes across the range of body sizes is small compared to other Onthophagus species. However, the scaling relationship between the thoracic horn and body size is best explained by a strongly sigmoid model. Only males above a certain body size threshold express a thoracic horn and males smaller than this threshold express no horn at all. We found a significant positive correlation between head and thoracic horn length residuals, contrary to what would be expected if a resource allocation tradeoff during larval development would influence the length of both horn types. Our results suggest that the scaling relationship between body size and horn length, and the developmental regulation underlying these scaling relationships, may be quite different for different horns, even though these horns may develop in the same individual. We discuss our results in the context of the developmental biology of secondary sexual traits in beetles. © 2004 The Linnean Society of London, Biological Journal of the Linnean Society, 2004, 83 , 473–480.     

Identification of an interleukin-1 beta binding protein in human plasma

A covalent cross-linking technique was used to bind iodinated interleukin-1 (IL1) alpha and beta to plasma proteins. One specific IL1 beta binding protein was observed, that when cross-linked to ¹²⁵I-ILl beta migrated to approximately 60 kDa on SDS-PAGE. The protein did not bind IL1 alpha. The 43 -kDa protein was partially purified using a wheat germ agglutinin affinity column. The isolated factor again specifically bound IL1 beta, and appeared to consist of single chain glycoprotein. The protein was heat stable and had a rapid association time with IL1 beta. This protein may be an important carrier molecule for IL1 beta in vivo.