Tpo1‐mediated spermine and spermidine export controls cell cycle delay and times antioxidant protein expression during the oxidative stress response

Synergistic impairment of the blood-brain barrier (BBB) induced by methamphetamine (METH) and HIV-Tat protein increases the risk of HIV-associated neurocognitive disorders (HAND) in HIV-positive METH abusers. Studies have shown that oxidative stress plays a vital role in METH- and HIV-Tat-induced damage to the BBB but have not clarified the mechanism. This study uses the human brain microvascular endothelial cell line hCMEC/D3 and tree shrews to investigate whether the transient receptor potential melastatin 2 (TRPM2) channel, a cellular effector of the oxidative stress, might regulate synergistic damage to the BBB caused by METH and HIV-Tat. We showed that METH and HIV-Tat damaged the BBB in vitro, producing abnormal cell morphology, increased apoptosis, reduced protein expression of the tight junctions (TJ) including Junctional adhesion molecule A (JAMA) and Occludin, and a junctional associated protein Zonula occludens 1 (ZO1), and increased the flux of sodium fluorescein (NaF) across the hCMEC/D3 cells monolayer. METH and HIV-Tat co-induced the oxidative stress response, reducing catalase (CAT), glutathione peroxidase (GSH-PX), and superoxide dismutase (SOD) activity, as well as increased reactive oxygen species (ROS) and malonaldehyde (MDA) level. Pretreatment with n-acetylcysteine amide (NACA) alleviated the oxidative stress response and BBB damage characterized by improving cell morphology, viability, apoptosis levels, TJ protein expression levels, and NaF flux. METH and HIV-Tat co-induced the activation and high protein expression of the TRPM2 channel, however, early intervention using 8-Bromoadenosine-5′-O-diphosphoribose (8-Br-ADPR), an inhibitor of TPRM2 channel, or TRPM2 gene knockdown attenuated the BBB damage. Oxidative stress inhibition reduced the activation and high protein expression of the TRPM2 channel in the in vitro model, which in turn reduced the oxidative stress response. Further, 8-Br-ADPR attenuated the effects of METH and HIV-Tat on the BBB in tree shrews—namely, down-regulated TJ protein expression and increased BBB permeability to Evans blue (EB) and NaF. In summary, the TRPM2 channel can regulate METH- and HIV-Tat-induced oxidative stress and BBB injury, giving the channel potential for developing drug interventions to reduce BBB injury and neuropsychiatric symptoms in HIV-infected METH abusers.

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17β-Estradiol alters oxidative damage and oxidative stress response protein expression in the mouse mammary gland

Molecular and Cellular Endocrinology ◽

10.1016/j.mce.2016.02.007 ◽

2016 ◽

Vol 426 ◽

pp. 11-21 ◽

Cited By ~ 4

Author(s):

Lisi Yuan ◽

Alicia K. Dietrich ◽

Yvonne S. Ziegler ◽

Ann M. Nardulli

Keyword(s):

Oxidative Stress ◽

Mammary Gland ◽

Stress Response ◽

Oxidative Damage ◽

Protein Expression ◽

Mouse Mammary Gland ◽

Oxidative Stress Response ◽

17Β Estradiol ◽

And Oxidative Stress

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Attachment of the Ubiquitin-Related Protein Urm1p to the Antioxidant Protein Ahp1p

Eukaryotic Cell ◽

10.1128/ec.2.5.930-936.2003 ◽

2003 ◽

Vol 2 (5) ◽

pp. 930-936 ◽

Cited By ~ 71

Author(s):

April S. Goehring ◽

David M. Rivers ◽

George F. Sprague

Keyword(s):

Oxidative Stress ◽

Saccharomyces Cerevisiae ◽

Stress Response ◽

Posttranslational Modification ◽

Oxidative Stress Response ◽

Nutrient Sensing ◽

Related Protein ◽

Antioxidant Protein ◽

Antioxidant Stress

ABSTRACT Urm1p is a ubiquitin-related protein that serves as a posttranslational modification of other proteins. Urm1p conjugation has been implicated in the budding process and in nutrient sensing. Here, we have identified the first in vivo target for the urmylation pathway as the antioxidant protein Ahp1p. The attachment of Urm1p to Ahp1p requires the E1 for the urmylation pathway, Uba4p. Loss of the urmylation pathway components results in sensitivity to a thiol-specific oxidant, as does loss of Ahp1p, implying that urmylation has a role in an oxidative-stress response. Moreover, treatment of cells with thiol-specific oxidants affects the abundance of Ahp1p-Urm1p conjugates. These results suggest that the conjugation of Urm1p to Ahp1p could regulate the function of Ahp1p in antioxidant stress response in Saccharomyces cerevisiae.

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DIGE-Based Protein Expression Analysis of B[a]P-Exposed Hepatoma Cells Reveals a Complex Stress Response Including Alterations in Oxidative Stress, Cell Cycle Control, and Cytoskeleton Motility at Toxic and Subacute Concentrations

Journal of Proteome Research ◽

10.1021/pr100723d ◽

2011 ◽

Vol 10 (2) ◽

pp. 379-393 ◽

Cited By ~ 12

Author(s):

Franziska Dautel ◽

Stefan Kalkhof ◽

Saskia Trump ◽

Jacob Michaelson ◽

Andreas Beyer ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Cycle ◽

Stress Response ◽

Protein Expression ◽

Expression Analysis ◽

Cell Cycle Control ◽

Hepatoma Cells ◽

Complex Stress

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Biological role, protein expression, subcellular localization, and oxidative stress response of paraoxonase 2 in the intestine of humans and rats

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00369.2007 ◽

2007 ◽

Vol 293 (6) ◽

pp. G1252-G1261 ◽

Cited By ~ 40

Author(s):

Emile Levy ◽

Karine Trudel ◽

Moise Bendayan ◽

Ernest Seidman ◽

Edgard Delvin ◽

...

Keyword(s):

Oxidative Stress ◽

Lipid Peroxidation ◽

Stress Response ◽

Subcellular Localization ◽

Protein Expression ◽

Oxidative Stress Response ◽

Butylated Hydroxytoluene ◽

Cell Fractionation ◽

Rat Intestine ◽

And Oxidative Stress

Oxidative stress is a cardinal manifestation of various intestinal disorders. However, very little knowledge is available on the intestine's inherent defense mechanisms against free radicals. This study was designed to determine the protein expression, subcellular localization and oxidative stress response of paraoxonase 2 (PON2), a member of a powerful antioxidant family in human and rat intestine. Biochemical and ultrastructural experiments all showed a substantial expression of PON2 in human and rat intestine. Western blot analysis disclosed higher levels of PON2 in the jejunum than in the duodenum, ileum, and colon. Cell fractionation revealed a predominant PON2 association with microsomes and lysosomes in the human jejunum, which differed from that in rats. PON2 was detected in the intestine as early as week 15 of gestation and was significantly increased by week 20. Iron ascorbate-mediated lipid peroxidation induced a marked decrease in PON2 expression in intestinal specimens coincidental to an abundant rise in malondialdehyde (MDA). On the other hand, preincubation with potent antioxidants, such as butylated hydroxytoluene, Trolox, and N-acetylcysteine, prevented iron-ascorbate-generating PON2 reduction in parallel with MDA suppression. Finally, the preincubation of permeabilized Caco-2 cells with purified PON2 led to a protection against iron-ascorbate-induced lipid peroxidation. These observations demonstrate that the human intestine is preferentially endowed with a marked PON2 expression compared with the rat intestine and this expression shows a developmental and intracellular pattern of distribution. Furthermore, our observations suggest PON2 protective effects against prooxidant stimuli in the small intestine.

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Proteomic signatures of acute oxidative stress response to paraquat in the mouse heart

10.1101/2020.05.29.124487 ◽

2020 ◽

Author(s):

Vishantie Dostal ◽

Silas D. Wood ◽

Cody T. Thomas ◽

Yu Han ◽

Edward Lau ◽

...

Keyword(s):

Oxidative Stress ◽

Stress Response ◽

Protein Expression ◽

Stress Responses ◽

Oxidative Stress Response ◽

Cardiac Response ◽

Differential Sensitivity ◽

Mouse Heart ◽

Rapid Reduction ◽

Proteome Changes

AbstractThe heart is sensitive to oxidative damage but a global view on how the cardiac proteome responds to oxidative stressors has yet to fully emerge. Using quantitative tandem mass spectrometry, we assessed the effects of acute exposure of the oxidative stress inducer paraquat on protein expression in mouse hearts. We observed widespread protein expression changes in the paraquat-exposed heart especially in organelle-containing subcellular fractions. During cardiac response to acute oxidative stress, proteome changes are consistent with a rapid reduction of mitochondrial metabolism, coupled with activation of multiple antioxidant proteins, reduction of protein synthesis and remediation of proteostasis. In addition to differential expression, we saw evidence of spatial reorganizations of the cardiac proteome including the translocation of hexokinase 2 to more soluble fractions. Treatment with the antioxidants Tempol and MitoTEMPO reversed many proteomic signatures of paraquat but this reversal was incomplete. We also identified a number of proteins with unknown function in the heart to be triggered by paraquat, suggesting they may have functions in oxidative stress response. Surprisingly, protein expression changes in the heart correlate poorly with those in the lung, consistent with differential sensitivity or stress response in these two organs. The results provide insights into oxidative stress responses in the heart and may avail the search for new therapeutic targets.

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