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Major Effect of Oxidative Stress on the Male, but Not Female, SP-A1 Type II Cell miRNome.

ABSTRACT: Pulmonary surfactant protein A (SP-A) plays an important role in surfactant metabolism and lung innate immunity. In humans there are two proteins, SP-A1 and SP-A2, encoded by SFTPA1 and SFTPA2, respectively, which are produced by the alveolar type II cells (T2C). We sought to investigate the differential influence of SP-A1 and SP-A2 in T2C miRNome under oxidative stress (OxS). SP-A knock out (KO) and hTG male and female mice expressing SP-A1 or SP-A2 as well as gonadectomized (Gx) mice were exposed to O₃-induced oxidative stress (OxS) or filtered air (FA). Expression of miRNAs and mRNAs was measured in the T2C of experimental animals. (a) In SP-A1 males after normalizing to KO males, significant changes were observed in the miRNome in terms of sex-OxS effects, with 24 miRNAs being differentially expressed under OxS. (b) The mRNA targets of the dysregulated miRNAs included Ago2, Ddx20, Plcg2, Irs1, Elf2, Jak2, Map2k4, Bcl2, Ccnd1, and Vhl. We validated the expression levels of these transcripts, and observed that the mRNA levels of all of these targets were unaffected in SP-A1 T2C but six of these were significantly upregulated in the KO (except Bcl2 that was downregulated). (c) Gondadectomy had a major effect on the expression of miRNAs and in three of the mRNA targets (Irs1, Bcl2, and Vhl). Ccnd1 was upregulated in KO regardless of Gx. (d) The targets of the significantly changed miRNAs are involved in several pathways including MAPK signaling pathway, cell cycle, anti-apoptosis, and other. In conclusion, in response to OxS, SP-A1 and male hormones appear to have a major effect in the T2C miRNome.

SUBMITTER: Noutsios GT

PROVIDER: S-EPMC6635478 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Major Effect of Oxidative Stress on the Male, but Not Female, SP-A1 Type II Cell miRNome.

Noutsios George T GT Thorenoor Nithyananda N Zhang Xuesheng X Phelps David S DS Umstead Todd M TM Durrani Faryal F Floros Joanna J

Frontiers in immunology 20190710

Pulmonary surfactant protein A (SP-A) plays an important role in surfactant metabolism and lung innate immunity. In humans there are two proteins, SP-A1 and SP-A2, encoded by <i>SFTPA1</i> and <i>SFTPA2</i>, respectively, which are produced by the alveolar type II cells (T2C). We sought to investigate the differential influence of SP-A1 and SP-A2 in T2C miRNome under oxidative stress (OxS). SP-A knock out (KO) and hTG male and female mice expressing SP-A1 or SP-A2 as well as gonadectomized (Gx) ...[more]

PMID: 31354704

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Project description:The trade-off between current reproductive effort and survival is a key concept of life history theory. A variety of studies support the existence of this trade-off but the underlying physiological mechanisms are not well-understood. Oxidative stress has been proposed as a potential mechanism underlying the observed inverse relationship between reproductive investment and lifespan. Prolonged fasting is associated with oxidative stress including increases in the production of reactive oxygen species, oxidative damage and inflammation.Northern elephant seals (NES) undergo prolonged fasts while maintaining high metabolic rates during breeding. We investigated NES of both sexes to assess oxidative stress associated with extended breeding fasts. We measured changes in the plasma activity or concentrations of markers for oxidative stress in 30 adult male and 33 adult female northern elephant seals across their 1-3 month breeding fasts. Markers assessed included a pro-oxidant enzyme, several antioxidant enzymes, markers for oxidative damage to lipids, proteins and DNA, and markers for systemic inflammation.Plasma xanthine oxidase (XO), a pro-oxidant enzyme that increases production of oxidative radicals, and several protective antioxidant enzymes increased over breeding in both sexes. Males showed increased oxidative damage to lipids and DNA and increased systemic inflammation, while oxidative damage to proteins declined across breeding. In contrast, females showed no oxidative damage to lipids or DNA or changes in inflammation, but showed increases in oxidative damage to proteins. XO activity, antioxidant enzymes, oxidative damage markers, and inflammatory markers were strongly correlated in males but these relationships were weaker or non-existent in females.NES provide evidence for oxidative stress as a physiological cost of reproduction in a capital breeding mammal. Both sexes strongly up-regulated antioxidant defenses during breeding. Despite this response, and in contrast to similar duration non-breeding fasts in previous studies on conspecifics, there was evidence of oxidative damage to tissues. These data demonstrate the utility of using plasma markers to examine oxidative stress but also suggest the necessity of measuring a broad suite of plasma markers to assess systemic oxidative stress.

Dataset Information

Major Effect of Oxidative Stress on the Male, but Not Female, SP-A1 Type II Cell miRNome.

Publications

Major Effect of Oxidative Stress on the Male, but Not Female, SP-A1 Type II Cell miRNome.

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