Mitochondrial homeostatic imbalance-mediated developmental toxicity to H2S in embryonic zebrafish

IF 7.6 2区 环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES
Yinai Liu , Yu Cao , Huiqi Li, Huanpeng Liu, Ting Chen, Qizhuan Lin, Changyong Gong, Fan Yu, Helei Cai, Libo Jin, Renyi Peng
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Abstract

Hydrogen sulfide (H2S) is a pervasive environmental and industrial pollutant that poses a substantial threat to human health. Even short-term exposure to H2S can result in severe respiratory and neurological damage. However, the underlying mechanisms of its biotoxicity remain unclear. Our study demonstrated that continuous exposure to 30 μM (1.02 ppm), whin environmentally H2S concentration range, results in notable developmental toxicity, including high mortality rates, morphological deformities, and behavioral abnormalities, in zebrafish larvae. Through transcriptomic analysis, examination of mitochondrial structure and function, and tissue and cellular staining, we found that H2S exposure disrupted mitochondrial dynamics, autophagy, and biogenesis, leading to an imbalance in mitochondrial homeostasis. This disruption induced oxidative stress and extensive apoptosis. Nitric oxide (NO) is a multifunctional signaling molecule known to target and regulate mitochondrial regeneration. In our study, we discovered that sodium nitroprusside (SNP), an NO donor, can activate the NO-sGC-cGMP signaling pathway. This activation improves the homeostatic regulation of mitochondrial dynamics, autophagy, and biogenesis, thereby enhancing mitochondrial function and effectively mitigating H2S-induced biotoxicity. Our research not only elucidates the biotoxicity mechanisms of H2S exposure but also provides valuable insights into potential therapeutic strategies that alleviate or eliminate its toxic effects.

Abstract Image

Abstract Image

胚胎斑马鱼线粒体稳态失衡介导的对H2S的发育毒性
硫化氢(H2S)是一种普遍存在的环境和工业污染物,对人类健康构成重大威胁。即使短期暴露于H2S也会导致严重的呼吸和神经损伤。然而,其生物毒性的潜在机制尚不清楚。我们的研究表明,持续暴露在30 μM (1.02 ppm)的环境H2S浓度范围内,会对斑马鱼幼虫产生显著的发育毒性,包括高死亡率、形态畸形和行为异常。通过转录组学分析、线粒体结构和功能检查以及组织和细胞染色,我们发现H2S暴露会破坏线粒体动力学、自噬和生物发生,导致线粒体稳态失衡。这种破坏诱导氧化应激和广泛的细胞凋亡。一氧化氮(NO)是一种已知的靶向和调节线粒体再生的多功能信号分子。在我们的研究中,我们发现硝普钠(SNP)作为NO供体可以激活NO- sgc - cgmp信号通路。这种激活改善了线粒体动力学、自噬和生物发生的稳态调节,从而增强线粒体功能,有效减轻h2s诱导的生物毒性。我们的研究不仅阐明了H2S暴露的生物毒性机制,而且为减轻或消除其毒性作用的潜在治疗策略提供了有价值的见解。
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来源期刊
Environmental Pollution
Environmental Pollution 环境科学-环境科学
CiteScore
16.00
自引率
6.70%
发文量
2082
审稿时长
2.9 months
期刊介绍: Environmental Pollution is an international peer-reviewed journal that publishes high-quality research papers and review articles covering all aspects of environmental pollution and its impacts on ecosystems and human health. Subject areas include, but are not limited to: • Sources and occurrences of pollutants that are clearly defined and measured in environmental compartments, food and food-related items, and human bodies; • Interlinks between contaminant exposure and biological, ecological, and human health effects, including those of climate change; • Contaminants of emerging concerns (including but not limited to antibiotic resistant microorganisms or genes, microplastics/nanoplastics, electronic wastes, light, and noise) and/or their biological, ecological, or human health effects; • Laboratory and field studies on the remediation/mitigation of environmental pollution via new techniques and with clear links to biological, ecological, or human health effects; • Modeling of pollution processes, patterns, or trends that is of clear environmental and/or human health interest; • New techniques that measure and examine environmental occurrences, transport, behavior, and effects of pollutants within the environment or the laboratory, provided that they can be clearly used to address problems within regional or global environmental compartments.
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