Bim mediates mitochondria‐regulated particulate matter‐induced apoptosis in alveolar epithelial cells

Abstract

We studied the role of Bim, a pro-apoptotic BCL-2 family member in Airborne particulate matter (PM 2.5 lm)-induced apoptosis in alveolar epithelial cells (AEC). PM induced AEC apoptosis by causing significant reduction of mitochondrial membrane potential and increase in caspase-9, caspase-3 and PARP-1 activation. PM upregulated pro-apoptotic protein Bim and enhanced translocation of Bim to the mitochondria. ShRNABim blocked PM-induced apoptosis by preventing activation of the mitochondrial death pathway suggesting a role of Bim in the regulation of mitochondrial pathway in AEC. Accordingly, we provide the evidence that Bim mediates PM-induced apoptosis via mitochondrial pathway.

Polycyclic aromatic hydrocarbon components contribute to the mitochondria-antiapoptotic effect of fine particulate matter on human bronchial epithelial cells via the aryl hydrocarbon receptor

“…Our results were obtained with a low concentration of PM 2.5 unlike previous publications performed with higher doses (e.g. 100 μg/cm 2 , [18]). Indeed, the standard dose used here (10 μg/cm 2 ) is a concentration which could mimic a five day exposure of PM 2.5 in the tracheobronchial region, considering that PM 2.5 mass deposition is 2.3 μg/cm 2 /24 h [11].…”

“…The activation of caspases or other proteases triggers the proteolysis of specific substrates involved into the final appearance of morphological features of apoptosis. Most publications dealing with toxicity of airborne particles showed an induction of apoptosis associated with ROS generation, ΔΨm drop, caspase-9 activation and DNA fragmentation [18].…”

Air pollution induces enhanced mitochondrial oxidative stress in cystic fibrosis airway epithelium

“…Furthermore, IB3‐1 CF cells were found to be highly sensitive to PM‐induced oxidative stress and apoptosis at much lower dose (25 μg/cm 2 ), as compared to previously reported PM‐induced apoptosis in alveolar epithelial cells (AEC) and A549 cells at the dose of 100 μg/cm 2 [6,17]. Therefore, a dose of 25 μg/cm 2 was used to perform all further experiments in IB3‐1 cells.…”

Lung injury after cigarette smoking is particle related

“…Numerous PM exposures activate the same kinases and pro-inflammatory transcription factors observed with cigarette smoke 115–118. Comparable to cigarette smoke, the same particles subsequently affect a release of inflammatory and apoptotic mediators 119–124…”