Altered mitochondrial biogenesis and its fusion gene expression is involved in the high-altitude adaptation of rat lung
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- 作者：Loganathan Chitra ; Rathanam Boopathy
- 关键词：ATP6/8 ; ATP synthetase6/8 ; Cyt b ; cytochrome b ; CO I/II/III ; cytochrome c oxidase I/II/III ; CS ; citrate synthase ; Drp-1 ; dynamin-related protein-1 ; ERR伪 ; estrogen-related receptor-伪 ; HH ; hypobaric hypoxia ; IHH ; intermittent hypobaric hypoxia ; Mfn1/2 ; mitofusin1/2 ; mtDNA ; mitochondrial DNA ; ND1 to 6* 4L ; NADH-dehydrogenase-ubiquinone reductase1 to 6* 4L ; nDNA ; nuclear DNA ; NRF1/2 ; nuclear respiratory factor 1/2 ; OXPHOS ; oxidative phosphorylation ; PGC-1伪 ; peroxisome proliferator-activated recep
- 刊名：Respiratory Physiology & Neurobiology
- 出版年：1 February, 2014
- 年：2014
- 卷：192
- 期：Complete
- 页码：74-84
- 全文大小：2180 K
文摘
Intermittent hypobaric hypoxia-induced preconditioning (IHH-PC) of rat favored the adaption of lungs to severe HH conditions, possibly through stabilization of mitochondrial function. This is based on the data generated on regulatory coordination of nuclear DNA-encoded mitochondrial biogenesis; dynamics, and mitochondrial DNA (mtDNA)-encoded oxidative phosphorylation (mtOXPHOS) genes expression. At 16th day after start of IHH-PC (equivalent to 5000 m, 6 h/d, 2 w of treatment), rats were exposed to severe HH stimulation at 9142 m for 6 h. The IHH-PC significantly counteracted the HH-induced effect of increased lung: water content; tissue damage; and oxidant injury. Further, IHH-PC significantly increased the mitochondrial number, mtDNA content and mtOXPHOS complex activity in the lung tissues. This observation is due to an increased expression of genes involved in mitochondrial biogenesis (PGC-1伪, ERR伪, NRF1, NRF2 and TFAM), fusion (Mfn1 and Mfn2) and mtOXPHOS. Thus, the regulatory pathway formed by PGC-1伪/ERR伪/Mfn2 axes is required for the mitochondrial adaptation provoked by IHH-PC regimen to counteract subsequent HH stress.