Inhibition of inducible nitric oxide synthase expression and nitric oxide production in plateau pika (Ochotona curzoniae) at high altitude on Qinghai-Tibet Plateau

Xie, Ling; Zhang, Xuze; Qi, Di; Guo, Xinyi; Pang, Bo; Du, Yurong; Zou, Xiaoyan; Guo, Sheng‐Ping; Zhao, Xinquan

doi:10.1016/j.niox.2014.02.009

Cited by 8 publications

(3 citation statements)

References 70 publications

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“…Cold and hypoxia are defining features of the Qinghai–Tibet Plateau environment, and plateau pika have developed tolerances to this harsh environment ( Xie et al, 2014 ; Wei et al, 2016 ). Consistent with previous studies that demonstrated that pika have tolerance to hypoxia and low-temperatures ( Yang et al, 2006 ; Zhu et al, 2018 ), a previous study showed that plateau pika can effectively endure extremely cold environments ( Li et al, 2001 ).…”

Section: Discussionmentioning

confidence: 99%

Differential Expression of Metabolism-Related Genes in Plateau Pika (Ochotona curzoniae) at Different Altitudes on the Qinghai–Tibet Plateau

Zhu

Zhong

et al. 2022

Front. Genet.

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According to life history theory, animals living in extreme environments have evolved specific behavioral and physiological strategies for survival. However, the genetic mechanisms underpinning these strategies are unclear. As the highest geographical unit on Earth, the Qinghai–Tibet Plateau is characterized by an extreme environment and climate. During long-term evolutionary processes, animals that inhabit the plateau have evolved specialized morphological and physiological traits. The plateau pika (Ochotona curzoniae), one of the native small mammals that evolved on the Qinghai–Tibet Plateau, has adapted well to this cold and hypoxic environment. To explore the genetic mechanisms underlying the physiological adaptations of plateau pika to extremely cold ambient temperatures, we measured the differences in resting metabolic rate (RMR) and metabolism-related gene expression in individuals inhabiting three distinct altitudes (i.e., 3,321, 3,663, and 4,194 m). Results showed that the body mass and RMR of plateau pika at high- and medium-altitudes were significantly higher than those at the low-altitude. The expression levels of peroxisome proliferator-activated receptor α (pparα), peroxisome proliferator-activated receptor-γ coactivator-1α (pgc-1α), and the PR domain-containing 16 (PRDM16) in white (WAT) and brown (BAT) adipose tissues of plateau pika from high- and medium-altitudes were significantly higher than in pika from the low-altitude region. The enhanced expression levels of pgc-1α and pparα genes in the WAT of pika at high-altitude showed that WAT underwent “browning” and increased thermogenic properties. An increase in the expression of uncoupling protein 1 (UCP1) in the BAT of pika at high altitude indicated that BAT increased their thermogenic properties. The gene expression levels of pparα and pgc-1α in skeletal muscles were significantly higher in high-altitude pika. Simultaneously, the expression of the sarcolipin (SLN) gene in skeletal muscles significantly increased in high-altitude pika. Our results suggest that plateau pika adapted to an extremely cold environment via browning WAT, thereby activating BAT and enhancing SLN expression to increase non-shivering thermogenesis. This study demonstrates that plateau pika can increase thermogenic gene expression and energy metabolism to adapt to the extreme environments on the plateau.

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Section: Discussionmentioning

confidence: 99%

Differential Expression of Metabolism-Related Genes in Plateau Pika (Ochotona curzoniae) at Different Altitudes on the Qinghai–Tibet Plateau

Zhu

Zhong

et al. 2022

Front. Genet.

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“…Animal models gave controversial results. On one hand, plateau pika (Ochotona curzoniae), a hypoxia-tolerant mammal that lives at 3000–5000 m/14.7–11.3 %O 2 on the Qinghai-Tibet Plateau, show reduced NOx compared to lower-altitude controls, indicating that NO production is suppressed at altitude [ 133 ]. On the other hand, newborn highland lambs show enhanced NO function compared to lowland controls, corresponding to increased RhoA expression in the lungs, which suggests that NO-mediated vasodilation is important to maintain the pulmonary vascular resistance [ 134 ].…”

Section: The Oxygen Cascadementioning

confidence: 99%

The Oxygen Cascade from Atmosphere to Mitochondria as a Tool to Understand the (Mal)adaptation to Hypoxia

Samaja¹,

Ottolenghi

2023

IJMS

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Hypoxia is a life-threatening challenge for about 1% of the world population, as well as a contributor to high morbidity and mortality scores in patients affected by various cardiopulmonary, hematological, and circulatory diseases. However, the adaptation to hypoxia represents a failure for a relevant portion of the cases as the pathways of potential adaptation often conflict with well-being and generate diseases that in certain areas of the world still afflict up to one-third of the populations living at altitude. To help understand the mechanisms of adaptation and maladaptation, this review examines the various steps of the oxygen cascade from the atmosphere to the mitochondria distinguishing the patterns related to physiological (i.e., due to altitude) and pathological (i.e., due to a pre-existing disease) hypoxia. The aim is to assess the ability of humans to adapt to hypoxia in a multidisciplinary approach that correlates the function of genes, molecules, and cells with the physiologic and pathological outcomes. We conclude that, in most cases, it is not hypoxia by itself that generates diseases, but rather the attempts to adapt to the hypoxia condition. This underlies the paradigm shift that when adaptation to hypoxia becomes excessive, it translates into maladaptation.

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“…Accordingly, uneven responses between pika species living at distinct elevations seem to reflect varying degrees of tolerance of alpine stresses (Sheafor, 2003;Xie et al, 2014). For example, Sheafor (2003) found that high-elevation American pikas Ochotona princeps have higher metabolic enzyme and cardiopulmonary tissue activities than do lowland northern pikas Ochotona hyperborea.…”

Section: Introductionmentioning

confidence: 99%

Divergent adaptations in resource‐use traits explain how pikas thrive on the roof of the world

Feijó

Wen

et al. 2020

Functional Ecology

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Life in extreme environments is possible through multilevel adaptations to physical and biotic stresses. At high elevations, species face numerous challenges, besides low oxygen levels, but previous studies have focused on genetic and physiological adaptations to chronic hypoxia while overlooking other key strategies for thriving in alpine landscapes. Here, we investigate resource‐use trait adaptations to extreme elevations using pikas as a model, lagomorphs distributed up to 6,200 m and reaching maximum diversity on the Qinghai‐Tibet plateau, the highest plateau on Earth. Specifically, we assess cranial evolution in pikas using geometric morphometric and phylogenetic comparative techniques to determine whether adaptations among high‐elevation biota shown at the molecular and physiological levels also occur in resource‐use traits. We further explore the roles of two contrasting lifestyles (burrowing and rocky‐dwelling) in cranial evolution. We found that alpine species exhibit striking phenotypic specialization to distinct microhabitats. Contrary to physiological and genetic adaptive convergence, we show that the cranium has undergone adaptive divergence likely reflecting past resource competition in highlands and long‐term association with alpine landscapes. Our analyses also reveal that the evolution of burrowing lifestyle allows high‐elevation pikas to explore novel niches and boosts their phenotypic diversification. In addition to cold and hypoxia tolerance, high cranial specialization, the appearance of burrowing habits and strong niche separation explain how pikas overcome alpine stresses and flourish on the highest plateau on Earth. By contrast, when moving to spatially complex and heterogeneous vegetation zonation, pikas exhibit generalist skull forms able to exploit diverse habitats. These findings mirror previously reported intraspecific patterns in mammals, suggesting a general morphological response in resource‐exploiting traits to cope with distinct selection pressures across elevation zones. Phenotypic diversity is further constrained by rocky habitats, resulting in convergent skulls. Our study highlights that adaptations to extreme environments occur at multiple levels of organization, but can lead to distinct evolutionary paths depending on which selective forces they respond to. The evolution of burrowing behaviour represents a landmark in the evolutionary history of pikas. We further show that rocky habitats impose strong ecological pressures, leading to convergent responses in resource‐use traits, which is rarely documented in mammals.

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Inhibition of inducible nitric oxide synthase expression and nitric oxide production in plateau pika (Ochotona curzoniae) at high altitude on Qinghai-Tibet Plateau

Cited by 8 publications

References 70 publications

Differential Expression of Metabolism-Related Genes in Plateau Pika (Ochotona curzoniae) at Different Altitudes on the Qinghai–Tibet Plateau

Differential Expression of Metabolism-Related Genes in Plateau Pika (Ochotona curzoniae) at Different Altitudes on the Qinghai–Tibet Plateau

The Oxygen Cascade from Atmosphere to Mitochondria as a Tool to Understand the (Mal)adaptation to Hypoxia

Divergent adaptations in resource‐use traits explain how pikas thrive on the roof of the world

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