The Role of Copper Oxide Nanomaterials on Ruta graveolens Physiological Response, and IRT1 and CAT Gene Expression

Hypoxia-inducible factors (HIFs) play an important role in mediating the physiological response to low oxygen environments. However, whether the expression of HIFs changes with age is unknown. In the present study, the effect of aging on HIF-1α, HIF-2α, HIF-3α and VEGF expression in the heart and lung of 30 Tibetan sheep that were adapted to hypoxia was evaluated. The 30 sheep were subdivided into groups of 10 animals that were 1, 2 or 6 years of age. Immunohistochemistry for HIF-1α, HIF-2α, HIF-3α and VEGF revealed that the immunostaining intensity of VEGF protein in the heart and lung was significantly higher than the intensity of immunostaining against the HIFs (p < 0.05). HIF-1α and HIF-2α protein translocated into the nucleus of cardiac muscle cells. However, immunostaining for HIF-3α was restricted to the cytoplasm of the myocardial cells. Immunostaining for HIF-1α, HIF-2α, HIF-3α and VEGF was detected within alveolar macrophages. The concentration of HIF-1α and HIF-2α was higher in the lung of 1-year-old than 6-year-old sheep (p < 0.05). In contrast, HIF-3α and VEGF immunostaining was most prominent in the hearts of the oldest sheep. However, when RT-PCR was used to evaluate RNA within the tissues, the expression of all four studied genes was higher in the lung than in the heart in the 1-year-old sheep (p < 0.05). Furthermore, VEGF and HIF-3α gene expression was higher in the heart from 1-year old than 6-year old sheep (p < 0.05). However, in the lung, HIF-1α and HIF-2α gene expression was lower in 1-year old than 6-year old sheep (p < 0.05). We conclude that HIF-3α and VEGF may play be important in how the heart responds to hypoxia. Additionally, HIF-1α and HIF-2α may have a role in the adaptation of the lung to hypoxia. The expression of these proteins in alveolar macrophages suggests a potential role of these cells in the physiological response to hypoxia. These results are useful in understanding how age influences the hypoxia adaption mechanisms of the heart and lung and may help to better understand chronic mountain sickness that is commonly observed in Tibetan people living on the Qinghai-Tibetan plateau.

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Role of small nuclear RNAs in eukaryotic gene expression

Essays in Biochemistry ◽

10.1042/bse0540079 ◽

2013 ◽

Vol 54 ◽

pp. 79-90 ◽

Cited By ~ 34

Author(s):

Saba Valadkhan ◽

Lalith S. Gunawardane

Keyword(s):

Gene Expression ◽

Protein Interactions ◽

Rna Stability ◽

Splice Sites ◽

Branch Site ◽

Small Nuclear Rnas ◽

Eukaryotic Gene Expression ◽

Eukaryotic Gene ◽

Rna Biogenesis

Eukaryotic cells contain small, highly abundant, nuclear-localized non-coding RNAs [snRNAs (small nuclear RNAs)] which play important roles in splicing of introns from primary genomic transcripts. Through a combination of RNA–RNA and RNA–protein interactions, two of the snRNPs, U1 and U2, recognize the splice sites and the branch site of introns. A complex remodelling of RNA–RNA and protein-based interactions follows, resulting in the assembly of catalytically competent spliceosomes, in which the snRNAs and their bound proteins play central roles. This process involves formation of extensive base-pairing interactions between U2 and U6, U6 and the 5′ splice site, and U5 and the exonic sequences immediately adjacent to the 5′ and 3′ splice sites. Thus RNA–RNA interactions involving U2, U5 and U6 help position the reacting groups of the first and second steps of splicing. In addition, U6 is also thought to participate in formation of the spliceosomal active site. Furthermore, emerging evidence suggests additional roles for snRNAs in regulation of various aspects of RNA biogenesis, from transcription to polyadenylation and RNA stability. These snRNP-mediated regulatory roles probably serve to ensure the co-ordination of the different processes involved in biogenesis of RNAs and point to the central importance of snRNAs in eukaryotic gene expression.

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