Mechanistic insight into airborne particulate matter PM10 as an environmental hazard for hemorrhagic stroke: Evidence from in vitro and in vivo studies

Article

作者: Lee, Chae Hwan ; Koh, Young Ho ; Seo, Minseok ; Lee, Jin Hyup ; Pack, Seung Pil ; Chang, Moon Han ; Cha, Hanvit

Airborne particulate matter less than 10 µm in diameter (PM10) is recognized as a significant environmental risk factor for hemorrhagic stroke (HS), as evidenced by epidemiological studies that link PM10 with the heightened cerebrovascular mortality related to HS. Nonetheless, the molecular mechanisms underlying this association remain unknown. Cerebral aneurysm (CA), an etiological factor of HS, is characterized by a bulge resulting from the abnormal loss of the muscular layer of a cerebral artery, comprising brain vascular endothelial cell (BVEC) and vascular smooth muscle cell (VSMC). BVEC exhibiting an inflammatory phenotype is critical for VSMC death within the cerebrovasculature. Here, we elucidate a molecular mechanism by which PM10 augments necroptotic death of VSMC as a consequence of intercellular effects arising from FasL inflammatory cytokine, which is derived from BVEC. Notably, BVEC exposed to PM10 upregulates FasL through ATM-NF-κB signaling, in response to oxidative DNA damage. This genotoxic stress is attributed to pro-oxidant action of aluminum, the prevalent element in PM10. Furthermore, respiratory exposure to PM10 in mice precipitates early onset of CA development through necroptotic VSMC death in cerebral artery, by activating FasL expression in BVEC. In conclusion, this study provides molecular evidence establishing a direct association between PM10 pollution and an elevated risk of stroke, particularly HS.

2024-11-01·Toxicology and Applied Pharmacology

PM10 dysregulates epithelial barrier function in human corneal epithelial cells that is restored by antioxidant SKQ1

Article

作者: Wright, Robert ; McClellan, Sharon A ; Somayajulu, Mallika ; Muhammed, Farooq ; Hazlett, Linda D ; Hazlett, Linda D. ; McClellan, Sharon A. ; Ibrahim, Ahmed

Exposure to airborne particulate <10 μm (PM₁₀) adversely affects the ocular surface. This study tested PM₁₀ on epithelial barrier integrity in immortalized human corneal epithelial cells (HCE-2) and mouse cornea, and whether antioxidant SKQ1 is restorative. HCE-2 were exposed to 100 μg/ml PM₁₀ ± SKQ1 for 24 h. An Electric Cell-Substrate Impedance Sensing (ECIS) system monitored the impact of PM₁₀. RT-PCR, western blotting and immunofluorescence measured levels of barrier and associated proteins, stanniocalcin 2 (STC2), and a kit measured total calcium. In vivo, female C57BL/6 mice were exposed to either control air or PM₁₀ (±SKQ1) in a whole-body exposure chamber, and barrier associated proteins tested. Tight junction and mucins proteins in the cornea were tested. In HCE-2, PM₀ vs control significantly reduced mRNA and protein levels of tight junction and adherence proteins, and mucins. ECIS data demonstrated that PM₁₀ vs control cells exhibited a significant decrease in epithelial barrier strength at 4000 Hz indicated by reduced impedance and resistance. PM₁₀ also upregulated STC2 protein and total calcium levels. In vivo, PM₁₀ vs control reduced zonula occludens 1 and mucins. SKQ1 pre-treatment reversed PM₁₀ effects both in vitro and in vivo. In conclusion, PM₁₀ exposure reduced tight junction and mucin proteins, and compromised the seal between cells in the corneal epithelium leading to decreased epithelial barrier strength. This effect was reversed by SKQ1. Since the corneal epithelium forms the first line of defense against air pollutants, including PM₁₀, preserving its integrity using antioxidants such as SKQ1 is crucial in reducing the occurrence of ocular surface disorders.

2024-05-01·Ecotoxicology and Environmental Safety

Particulate matter (PM10) exacerbates on MK-801-induced schizophrenia-like behaviors through the inhibition of ERK-CREB-BDNF signaling pathway

Article

作者: Kim, Dong Hyun ; Choi, Yu-Yeong ; Kim, Hyun-Jeong ; An, Ju-Yeon ; Kim, So-Yeon ; Mony, Tamanna Jahan ; Cho, So-Young ; Bae, Ho Jung ; Cho, Ye Eun ; Choi, Seung-Hyuk ; Park, Se Jin

Particulate matter (PM), released into the air by a variety of natural and human activities, is a key indicator of air pollution. Although PM is known as the extensive health hazard to affect a variety of illness, few studies have specifically investigated the effects of PM₁₀ exposure on schizophrenic development. In the present study, we aimed to investigate the impact of PM₁₀ on MK-801, N-methyl-D-aspartate (NMDA) receptor antagonist, induced schizophrenia-like behaviors in C57BL/6 mouse. Preadolescent mice were exposed PM₁₀ to 3.2 mg/m³ concentration for 4 h/day for 2 weeks through a compartmentalized whole-body inhalation chamber. After PM₁₀ exposure, we conducted behavioral tests during adolescence and adulthood to investigate longitudinal development of schizophrenia. We found that PM₁₀ exacerbated schizophrenia-like behavior, such as psychomotor agitation, social interaction deficits and cognitive deficits at adulthood in MK-801-induced schizophrenia animal model. Furthermore, the reduced expression levels of brain-derived neurotrophic factor (BDNF) and the phosphorylation of BDNF related signaling molecules, extracellular signal-regulated kinase (ERK) and cAMP response element-binding protein (CREB), were exacerbated by PM₁₀ exposure in the adult hippocampus of MK-801-treated mice. Thus, our present study demonstrates that exposure to PM₁₀ in preadolescence exacerbates the cognitive impairment in animal model of schizophrenia, which are considered to be facilitated by the decreased level of BDNF through reduced ERK-CREB expression.

100 项与 PM-10 (MedImmune) 相关的药物交易

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