Browsing by Subject "Anoxia"

Now showing 1 - 3 of 3
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    Hydrogen Sulfide as an Oxygen Sensor
    (Mary Ann Liebert, Inc., 2014-05-07) Olson, Kenneth R.; IU School of Medicine, South Bend
    Significance: Although oxygen (O2)-sensing cells and tissues have been known for decades, the identity of the O2-sensing mechanism has remained elusive. Evidence is accumulating that O2-dependent metabolism of hydrogen sulfide (H2S) is this enigmatic O2 sensor. Recent Advances: The elucidation of biochemical pathways involved in H2S synthesis and metabolism have shown that reciprocal H2S/O2 interactions have been inexorably linked throughout eukaryotic evolution; there are multiple foci by which O2 controls H2S inactivation, and the effects of H2S on downstream signaling events are consistent with those activated by hypoxia. H2S-mediated O2 sensing has been demonstrated in a variety of O2-sensing tissues in vertebrate cardiovascular and respiratory systems, including smooth muscle in systemic and respiratory blood vessels and airways, carotid body, adrenal medulla, and other peripheral as well as central chemoreceptors. Critical Issues: Information is now needed on the intracellular location and stoichometry of these signaling processes and how and which downstream effectors are activated by H2S and its metabolites. Future Directions: Development of specific inhibitors of H2S metabolism and effector activation as well as cellular organelle-targeted compounds that release H2S in a time- or environmentally controlled way will not only enhance our understanding of this signaling process but also provide direction for future therapeutic applications. Antioxid. Redox Signal. 22, 377–397. “Nothing in Biology Makes Sense Except in the Light of Evolution” —Theodosius Dobzhansky (29)
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    Quantifying the Biogeochemical Impact of Land Plant Expansion in the Mid Devonian and Implications in Marine Anoxic Events
    (2022-12) Smart, Matthew Stephen; Filippelli, Gabriel; Gilhooly, William III; Barth, Andrew; Wilson, Jeffrey
    The evolution of land plant root systems occurred stepwise throughout the Devonian, with the first evidence of complex root systems appearing in the mid-Givetian. This biological innovation provided an enhanced pathway for the transfer of terrestrial phosphorus (P) to the marine system via weathering and erosion. This enhancement is consistent with paleosol records and has led to hypotheses about the causes of marine eutrophication and mass extinctions during the Devonian. To gain insight into the transport of P between terrestrial and marine domains, presented here are geochemical records from a survey of Middle and Late Devonian lacustrine and near lacustrine sequences that span some of these key marine extinction intervals. Root innovation is hypothesized to have enhanced P delivery and results from multiple Devonian sequences from Euramerica show evidence of a net loss of P from terrestrial sources coincident with the appearance of early progymnosperms. Evidence from multiple Middle to Late Devonian sites (from Greenland and northern Scotland/Orkney), reveal a near-identical net loss of P. Nitrogen and Carbon isotopes from a subset of these lakes confirm elevated input of terrestrial plant material concurrent with P perturbations. Terrestrial P input appears to be episodic in nature, suggesting land plant expansion was driven by an external catalyst in the study region. All sites analyzed are temporally proximal to significant marine extinctions, including precise correlation with the Kačák extinction event and the two pulses associated with the Frasnian-Famennian (F/F) mass extinction. The episodic expansion of terrestrial plants appears to be tied to variations in regional and global climate, and in the case of the F/F extinction, also to atmospheric changes associated with large scale volcanism. Using P data presented here as an input into an Earth system model of the coupled C-N-P-O2-S biogeochemical cycles shows that globally scaled riverine phosphorus export during the Frasnian-Famennian mass extinction generates widespread marine anoxia consistent with the geologic record. While timing precludes land plants as an initiating mechanism in the F/F extinction, these results suggest they are implicated in every marine extinction event in the Mid to Late Devonian.
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    Tip110 Regulates the Cross Talk between p53 and Hypoxia-Inducible Factor 1α under Hypoxia and Promotes Survival of Cancer Cells
    (MCB, 2015-07) Timani, Khalid Amine; Liu, Ying; Fan, Yan; Mohammad, Khalid S.; He, Johnny J.; Department of Medicine, IU School of Medicine
    Hypoxia often occurs under various physiological and pathophysiological conditions, including solid tumors; it is linked to malignant transformation, metastatic progression, and treatment failure or resistance. Tip110 protein plays important roles in several known physiological and pathophysiological processes, including cancers. Thus, in the present study we investigated the regulation of Tip110 expression under hypoxia. Hypoxia led to Tip110 protein degradation through the ubiquitin-proteasome system. Under hypoxia, Tip110 stabilized p53, which in return destabilized Tip110. In addition, Tip110 regulated hypoxia-inducible factor 1α (HIF-1α), likely through enhancement of its protein stability. Furthermore, Tip110 upregulated p300, a known coactivator for both p53 and HIF-1α. Expression of a p53(22/23) mutant deficient in p300 binding accelerated Tip110 degradation under hypoxia. Tip110 knockdown resulted in the inhibition of cell proliferation and cell death in the presence of p53. Finally, significantly less Tip110, p53, and HIF-1α was detected in the hypoxic region of bone metastasis tumors in a mouse model of human melanoma cells. Taken together, these results suggest Tip110 is an important mediator in the cross talk between p53 and HIF-1α in response to hypoxic stress.