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  • 1
    Online Resource
    Online Resource
    Shorter telomere length, higher telomerase activity in association with tankyrase gene polymorphism contribute to high-altitude pulmonary edema
    Oxford University Press (OUP) ; 2020
    In:  Human Molecular Genetics Vol. 29, No. 18 ( 2020-11-04), p. 3094-3106
    Details
    In: Human Molecular Genetics, Oxford University Press (OUP), Vol. 29, No. 18 ( 2020-11-04), p. 3094-3106
    Abstract: High-altitude pulmonary edema (HAPE) is a noncardiogenic form of pulmonary edema, which is induced upon exposure to hypobaric hypoxia at high altitude (HA). Hypobaric hypoxia generates reactive oxygen species that may damage telomeres and disturb normal physiological processes. Telomere complex comprises of multiple proteins, of which, tankyrase (TNKS) is actively involved in DNA damage repairs. We hence investigated the association of TNKS and telomeres with HAPE to delineate their potential role at HA. The study was performed in three groups, High-altitude pulmonary edema patients (HAPE-p, n = 200), HAPE-resistant sojourners (HAPE-r, n = 200) and highland permanent healthy residents (HLs, n = 200). Variants of TNKS were genotyped using polymerase chain reaction–restriction fragment length polymorphism. Plasma TNKS level was estimated using enzyme-linked immunosorbent assay, expression of TNKS and relative telomere length were assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and telomerase activity was assessed by the telomere repeat amplification protocol assay. TNKS poly-ADP ribosylates the telomere-repeat factor (TRF), which is a negative regulator of telomere length. Consequently, TRF expression was also measured by RT-qPCR. The TNKS heterozygotes rs7015700GA were prevalent in HLs compared to the HAPE-p and HAPE-r. The plasma TNKS was significantly decreased in HAPE-p than HAPE-r (P = 0.006). TNKS was upregulated 9.27 folds in HAPE-p (P = 1.01E-06) and downregulated in HLs by 3.3 folds (P = 0.02). The telomere length was shorter in HAPE-p compared to HAPE-r (P = 0.03) and HLs (P = 4.25E-4). The telomerase activity was significantly higher in HAPE-p compared to both HAPE-r (P = 0.01) and HLs (P = 0.001). HAPE-p had the lowest TNKS levels (0.186 ± 0.031 ng/μl) and the highest telomerase activity (0.0268 amoles/μl). The findings of the study indicate the association of TNKS and telomeres with HA adaptation/maladaptation.
    Type of Medium: Online Resource
    ISSN: 0964-6906 , 1460-2083
    URL: Article
    DOI: 10.1093/hmg/ddaa205
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 1474816-2
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    Probable role of β2-adrenergic receptor gene haplotype in high-altitude pulmonary oedema : ADRB2 haplotypes in HAPE
    Wiley ; 2010
    In:  Respirology Vol. 15, No. 4 ( 2010-03-19), p. 651-658
    Details
    In: Respirology, Wiley, Vol. 15, No. 4 ( 2010-03-19), p. 651-658
    Type of Medium: Online Resource
    ISSN: 1323-7799 , 1440-1843
    URL: Issue
    URL: Article
    DOI: 10.1111/res.2010.15.issue-4
    DOI: 10.1111/j.1440-1843.2010.01757.x
    Language: English
    Publisher: Wiley
    Publication Date: 2010
    detail.hit.zdb_id: 2010720-1
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  • 3
    Online Resource
    Online Resource
    DataSheet1.pdf
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 13 ( 2022-5-20)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-5-20)
    Abstract: Dexamethasone can be taken prophylactically to prevent hypobaric hypoxia-associated disorders of high-altitude. While dexamethasone-mediated protection against high-altitude disorders has been clinically evaluated, detailed sex-based mechanistic insights have not been explored. As part of our India-Leh-Dexamethasone-expedition-2020 (INDEX 2020) programme, we examined the phenotype of control ( n = 14) and dexamethasone ( n = 13) groups, which were airlifted from Delhi (∼225 m elevation) to Leh, Ladakh (∼3,500 m), India, for 3 days. Dexamethasone 4 mg twice daily significantly attenuated the rise in blood pressure, heart rate, pulmonary pressure, and drop in SaO 2 resulting from high-altitude exposure compared to control-treated subjects. Of note, the effect of dexamethasone was substantially greater in women than in men, in whom the drug had relatively little effect. Thus, for the first time, this study shows a sex-biased regulation by dexamethasone of physiologic parameters resulting from the hypoxic environment of high-altitude, which impacts the development of high-altitude pulmonary hypertension and acute mountain sickness. Future studies of cellular contributions toward sex-specific regulation may provide further insights and preventive measures in managing sex-specific, high-altitude–related disorders.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2022.873867
    DOI: 10.3389/fphar.2022.873867.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 4
    Online Resource
    Online Resource
    Respiratory tract infection: an unfamiliar risk factor in high-altitude pulmonary edema
    Oxford University Press (OUP) ; 2022
    In:  Briefings in Functional Genomics ( 2022-12-10)
    Details
    In: Briefings in Functional Genomics, Oxford University Press (OUP), ( 2022-12-10)
    Abstract: The dramatic changes in physiology at high altitude (HA) as a result of the characteristic hypobaric hypoxia condition can modify innate and adaptive defense mechanisms of the body. As a consequence, few sojourners visiting HA with mild or asymptomatic infection may have an enhanced susceptibility to high-altitude pulmonary edema (HAPE), an acute but severe altitude sickness. It develops upon rapid ascent to altitudes above 2500 m, in otherwise healthy individuals. Though HAPE has been studied extensively, an elaborate exploration of the HA disease burden and the potential risk factors associated with its manifestation are poorly described. The present review discusses respiratory tract infection (RTI) as an unfamiliar but important risk factor in enhancing HAPE susceptibility in sojourners for two primary reasons. First, the symptoms of RTI s resemble those of HAPE. Secondly, the imbalanced pathways contributing to vascular dysfunction in HAPE also participate in the pathogenesis of the infectious processes. These pathways have a crucial role in shaping host response against viral and bacterial infections and may further worsen the clinical outcomes at HA. Respiratory tract pathogenic agents, if screened in HAPE patients, can help in ascertaining their role in disease risk and also point toward their association with the disease severity. The microbial screenings and identifications of pathogens with diseases are the foundation for describing potential molecular mechanisms underlying host response to the microbial challenge. The prior knowledge of such infections may predict the manifestation of disease etiology and provide better therapeutic options.
    Type of Medium: Online Resource
    ISSN: 2041-2649 , 2041-2657
    URL: Article
    DOI: 10.1093/bfgp/elac048
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2079121-5
    detail.hit.zdb_id: 2540929-3
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  • 5
    Online Resource
    Online Resource
    CYBA and GSTP1 variants associate with oxidative stress under hypobaric hypoxia as observed in high-altitude pulmonary oedema
    Portland Press Ltd. ; 2012
    In:  Clinical Science Vol. 122, No. 6 ( 2012-03-01), p. 299-311
    Details
    In: Clinical Science, Portland Press Ltd., Vol. 122, No. 6 ( 2012-03-01), p. 299-311
    Abstract: HAPE (high-altitude pulmonary oedema) is characterized by pulmonary hypertension, vasoconstriction and an imbalance in oxygen-sensing redox switches. Excess ROS (reactive oxygen species) contribute to endothelial damage under hypobaric hypoxia, hence the oxidative-stress-related genes CYBA (cytochrome b−245 α polypeptide) and GSTP1 (glutathione transferase Pi 1) are potential candidate genes for HAPE. In the present study, we investigated the polymorphisms −930A/G and H72Y (C/T) of CYBA and I105V (A/G) and A114V (C/T) of GSTP1, individually and in combination, in 150 HAPE-p (HAPE patients), 180 HAPE-r (HAPE-resistant lowland natives) and 180 HLs (healthy highland natives). 8-Iso-PGF2α (8-iso-prostaglandin F2α) levels were determined in plasma and were correlated with individual alleles, genotype, haplotype and gene–gene interactions. The relative expression of CYBA and GSTP1 were determined in peripheral blood leucocytes. The genotype distribution of −930A/G, H72Y (C/T) and I105V (A/G) differed significantly in HAPE-p compared with HAPE-r and HLs (P≤0.01). The haplotypes G-C of −930A/G and H72Y (C/T) in CYBA and G-C and G-T of I105V (A/G) and A114V (C/T) in GSTP1 were over-represented in HAPE-p; in contrast, haplotypes A-T of −930A/G and H72Y (C/T) in CYBA and A-C of I105V (A/G) and A114V (C/T) in GSTP1 were over-represented in HAPE-r and HLs. 8-Iso-PGF2α levels were significantly higher in HAPE-p and in HLs than in HAPE-r (P=2.2×10−16 and 1.2×10−14 respectively) and the expression of CYBA and GSTP1 varied differentially (P & lt;0.05). Regression analysis showed that the risk alleles G, C, G and T of −930A/G, H72Y (C/T), I105V (A/G) and A114V (C/T) were associated with increased 8-iso-PGF2α levels (P & lt;0.05). Interaction between the two genes revealed over-representation of most of the risk-allele-associated genotype combinations in HAPE-p and protective-allele-associated genotype combinations in HLs. In conclusion, the risk alleles of CYBA and GSTP1, their haplotypes and gene–gene interactions are associated with imbalanced oxidative stress and, thereby, with high-altitude adaptation and mal-adaptation.
    Type of Medium: Online Resource
    ISSN: 0143-5221 , 1470-8736
    URL: Article
    DOI: 10.1042/CS20110205
    Language: English
    Publisher: Portland Press Ltd.
    Publication Date: 2012
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  • 6
    Online Resource
    Online Resource
    Elevated Vasodilatory Cyclases and Shorter Telomere Length Contribute to High-Altitude Pulmonary Edema
    Mary Ann Liebert Inc ; 2018
    In:  High Altitude Medicine & Biology Vol. 19, No. 1 ( 2018-03), p. 60-68
    Details
    In: High Altitude Medicine & Biology, Mary Ann Liebert Inc, Vol. 19, No. 1 ( 2018-03), p. 60-68
    Type of Medium: Online Resource
    ISSN: 1557-8682
    URL: Article
    DOI: 10.1089/ham.2017.0136
    Language: English
    Publisher: Mary Ann Liebert Inc
    Publication Date: 2018
    detail.hit.zdb_id: 2023581-1
    SSG: 31
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  • 7
    Online Resource
    Online Resource
    Structural and functional alterations of nitric oxide synthase 3 due to missense variants associate with high-altitude pulmonary edema through dynamic study
    Informa UK Limited ; 2021
    In:  Journal of Biomolecular Structure and Dynamics Vol. 39, No. 1 ( 2021-01-02), p. 294-309
    Details
    In: Journal of Biomolecular Structure and Dynamics, Informa UK Limited, Vol. 39, No. 1 ( 2021-01-02), p. 294-309
    Type of Medium: Online Resource
    ISSN: 0739-1102 , 1538-0254
    URL: Article
    DOI: 10.1080/07391102.2019.1711190
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2021
    detail.hit.zdb_id: 2085732-9
    SSG: 12
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  • 8
    Online Resource
    Online Resource
    Hypobaric hypoxia drives selection of altitude-associated adaptative alleles in the Himalayan population
    Elsevier BV ; 2024
    In:  Science of The Total Environment Vol. 913 ( 2024-02), p. 169605-
    Details
    In: Science of The Total Environment, Elsevier BV, Vol. 913 ( 2024-02), p. 169605-
    Type of Medium: Online Resource
    ISSN: 0048-9697
    URL: Article
    DOI: 10.1016/j.scitotenv.2023.169605
    RVK:
    AR 10100
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2024
    detail.hit.zdb_id: 1498726-0
    detail.hit.zdb_id: 121506-1
    SSG: 12
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  • 9
    Online Resource
    Online Resource
    The Telomere-Telomerase System Is Detrimental to Health at High-Altitude
    MDPI AG ; 2023
    In:  International Journal of Environmental Research and Public Health Vol. 20, No. 3 ( 2023-01-20), p. 1935-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 20, No. 3 ( 2023-01-20), p. 1935-
    Abstract: The hypobaric-hypoxia environment at high-altitude (HA, 〉 2500 m) may influence DNA damage due to the production of reactive molecular species and high UV radiation. The telomere system, vital to chromosomal integrity and cellular viability, is prone to oxidative damages contributing to the severity of high-altitude disorders such as high-altitude pulmonary edema (HAPE). However, at the same time, it is suggested to sustain physical performance. This case-control study, comprising 210 HAPE-free (HAPE-f) sojourners, 183 HAPE-patients (HAPE-p) and 200 healthy highland natives (HLs) residing at ~3500 m, investigated telomere length, telomerase activity, and oxidative stress biomarkers. Fluidigm SNP genotyping screened 65 single nucleotide polymorphisms (SNPs) in 11 telomere-maintaining genes. Significance was attained at p ≤ 0.05 after adjusting for confounders and correction for multiple comparisons. Shorter telomere length, decreased telomerase activity and increased oxidative stress were observed in HAPE patients; contrarily, longer telomere length and elevated telomerase activity were observed in healthy HA natives compared to HAPE-f. Four SNPs and three haplotypes are associated with HAPE, whereas eight SNPs and nine haplotypes are associated with HA adaptation. Various gene-gene interactions and correlations between/among clinical parameters and biomarkers suggested the presence of a complex interplay underlining HAPE and HA adaptation physiology. A distinctive contribution of the telomere-telomerase system contributing to HA physiology is evident in this study. A normal telomere system may be advantageous in endurance training.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph20031935
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2175195-X
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  • 10
    Online Resource
    Online Resource
    EGLN1 variants influence expression and S a O 2 levels to associate with high-altitude pulmonary oedema and adaptation
    Portland Press Ltd. ; 2013
    In:  Clinical Science Vol. 124, No. 7 ( 2013-04-01), p. 479-489
    Details
    In: Clinical Science, Portland Press Ltd., Vol. 124, No. 7 ( 2013-04-01), p. 479-489
    Abstract: EGLN1 [encoding HIF (hypoxia-inducible factor)-prolyl hydroxylase 2] plays a pivotal role in the HIF pathway and has emerged as one of the most intriguing genes with respect to physiology at HA (high altitude). EGLN1, being an actual oxygen sensor, appears to have a potential role in the functional adaptation to the hypobaric hypoxic environment. In the present study, we screened 30 polymorphisms of EGLN1, evaluated its gene expression and performed association analyses. In addition, the role of allelic variants in altering TF (transcription factor)-binding sites and consequently the replacement of TFs at these loci was also investigated. The study was performed in 250 HAPE-p [HAPE (HA pulmonary oedema)-patients] , 210 HAPE-f (HAPE-free controls) and 430 HLs (healthy Ladakhi highland natives). The genotypes of seven polymorphisms, rs1538664, rs479200, rs2486729, rs2790879, rs480902, rs2486736 and rs973252, differed significantly between HAPE-p and HAPE-f (P & lt;0.008). The genotypes AA, TT, AA, GG, CC, AA and GG of rs1538664, rs479200, rs2486729, rs2790879, rs480902, rs2486736 and rs973252, prevalent in HAPE-p, were identified as risk genotypes and their counterpart homozygotes, prevalent in HLs, were identified as protective. EGLN1 expression was up-regulated 4.56-fold in HAPE-p (P=0.0084). The risk genotypes, their haplotypes and interacting genotypes were associated with up-regulated EGLN1 expression (P & lt;0.05). Similarly, regression analysis showed that the risk alleles and susceptible haplotypes were associated with decreased SaO2 (arterial oxygen saturation) levels in the three groups. The significant inverse correlation of SaO2 levels with PASP (pulmonary artery systolic pressure) and EGLN1 expression and the association of these polymorphisms with SaO2 levels and EGLN1 expression contributed to uncovering the molecular mechanism underlying hypobaric hypoxic adaptation and maladaptation.
    Type of Medium: Online Resource
    ISSN: 0143-5221 , 1470-8736
    URL: Article
    DOI: 10.1042/CS20120371
    Language: English
    Publisher: Portland Press Ltd.
    Publication Date: 2013
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