In:
Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 136, No. suppl_1 ( 2017-11-14)
Abstract:
Rationale: Human adaptation to high altitude hypoxia can potentially enlighten us for better therapeutic modalities for sea level diseases that involve hypoxia and ischemia in their pathogenesis. Using whole genome sequencing, we identified LIPE (Lipase E, Hormone Sensitive Type), as a candidate gene involved in HA adaptation. This gene is highly conserved and the ortholog in Drosophila i.e., Hsl , when globally knocked down and tested for hypoxia tolerance, significantly improves survival rates in low oxygen. Objective: To understand the hypoxia tolerance mechanism in Hsl- knockdown Drosophila . Methods and Results: We knocked down Hsl in individual tissue-types by crossing tissue specific Gal4 drivers with UAS- RNAi(Hsl) lines. To elucidate its potential role in hypoxia tolerance, we measured the eclosion rate (%) at 5% O 2 and compared with controls kept at room air (21% O 2 ). Remarkably, the eclosion rate for Hsl , at 5% O 2 , when knocked down specifically in heart (UAS- RNAi(Hsl) X Hand-Gal4 ) was significantly higher (86.02%; P 〈 0.05) when compared to the background controls (42.2% for w1118 , 50.06% for Hand-Gal4 and 39.72% for UAS- RNAi(Hsl) ). Conclusion: These data indicate that a lower level of Hsl in the heart significantly improves hypoxia tolerance in Drosophila . Interestingly, also during cardiac-ischemic-hypoxia, the cardiomyocytes strategically knockdown LIPE , preventing lipid metabolism and therefore reduce oxygen consumption when the supply is limited.
Type of Medium:
Online Resource
ISSN:
0009-7322
,
1524-4539
DOI:
10.1161/circ.136.suppl_1.21066
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2017
detail.hit.zdb_id:
1466401-X
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