Therapeutic potential of arachidonyl trifluromethyl ketone, a cytosolic phospholipaseA2 IVA specific inhibitor, in cigarette smoke condensate-induced pathological conditions in alveolar type I &amp; II epithelial cells

Kumar, Subodh; Sharma, Shubham; Kaushik, Gaurav; Avti, Pramod K.; Pandey, Satish Kumar; Sarma, Phulen; Medhi, Bikash; Khanduja, Krishan Lal

doi:10.1016/j.tiv.2018.09.013

Cited by 7 publications

(3 citation statements)

References 32 publications

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“…Data collected by the IVIS illustrated that the majority of CL‐MOFs‐A488 degraded at 72 h (Figure S3G, Supporting Information). The cyto‐compatibility of CL‐MOFs‐A488 was confirmed on Type I alveolar epithelial cells (WI26‐VA4), [ 16 ] Type II alveolar epithelial cells (A549), alveolar macrophages (MHS) and Tracheal epithelial cells (Calu‐3). The cell counting kit‐8 (CCK‐8) assay and lactate dehydrogenase (LDH) release assay confirmed the biocompatibility of CL‐MOFs‐A488 (Figure 3G,H).…”

Section: Resultsmentioning

confidence: 99%

Multiscale Co‐reconstruction of Lung Architectures and Inhalable Materials Spatial Distribution

et al. 2021

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The effective pulmonary deposition of inhaled particulate carriers loaded with drugs is a prerequisite for therapeutic effects of drug delivery via inhalation route. Revealing the sophisticated lung scaffold and intrapulmonary distribution of particles at three-dimensional (3D), in-situ, and single-particle level remains a fundamental and critical challenge for dry powder inhalation in pre-clinical research. Here, taking advantage of the micro optical sectioning tomography system, the high-precision cross-scale visualization of entire lung anatomy is obtained. Then, co-localized lung-wide datasets of both cyto-architectures and fluorescent particles are collected at full scale with the resolution down to individual particles. The precise spatial distribution pattern reveals the region-specific distribution and structure-associated deposition of the inhalable particles in lungs, which is undetected by previous methods. Overall, this research delivers comprehensive and high-resolution 3D detection of pulmonary drug delivery vectors and provides a novel strategy to evaluate materials distribution for drug delivery.

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Section: Resultsmentioning

confidence: 99%

Multiscale Co‐reconstruction of Lung Architectures and Inhalable Materials Spatial Distribution

et al. 2021

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“…Genetically modified immortalized human lung cells (WI26VA4) and human lung adenocarcinoma cells (A549) were used in the present study. In literature, WI26 and A549 cells have been used as in vitro model of type-I and type II human alveolar epithelial cells, − respectively, to study the effect of various toxicants including metal oxide nanoparticles, biomolecules, and drugs. , These cells were procured from European Collection of Authenticated Cell Cultures, cultured in Dulbecco’s modified Eagle’s medium supplemented with 10% fetal calf serum, 2 mM glutamine, and penicillin–streptomycin. Cells were seeded at desired cell density in triplicates for treatment groups and placed in a CO 2 incubator.…”

Section: Materials and Methodsmentioning

confidence: 99%

Thorium Alters Lung Surfactant Protein Expression in Alveolar Epithelial Cells: In Vitro and In Vivo Investigation

Das,

Ali,

Shetake

et al. 2024

Environ. Sci. Technol.

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Thorium-232 (Th), the most abundant naturally occurring nuclear fuel, has been identified as a sustainable source of energy. In view of its large-scale utilization and human evidence of lung disorders and carcinogenicity, it is imperative to understand the effect of Th exposure on lung cells. The present study investigated the effect of Th-dioxide (1–100 μg/mL, 24–48 h) on expression of surfactant proteins (SPs) (SP-A, SP-B, SP-C, and SP-D, which are essential to maintain lung’s surface tension and host-defense) in human lung cells (WI26 and A549), representative of alveolar cell type-I and type-II, respectively. Results demonstrated the inhibitory effect of Th on transcriptional expression of SP-A, SP-B, and SP-C. However, Th promoted the mRNA expression of SP-D in A549 and reduced its expression in WI26. To a significant extent, the effect of Th on SPs was found to be in accordance with their protein levels. Moreover, Th exposure altered the extracellular release of SP-D/A from A549, which remained unaltered in WI26. Our results suggested the differential role of oxidative stress and ATM and HSP90 signaling in Th-induced alterations of SPs. These effects of Th were found to be consistent in lung tissues of mice exposed to Th aerosols, suggesting a potential role of SPs in Th-associated lung disorders.

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“…In studies using cell and animal models, arachidonyl trifluoromethyl ketone (AACOCF3 or ATK) has been successfully used to suppress cPLA2 activity and production of eicosanoids [ 17 , 23 , 24 ]. AACOCF3 also mitigates cPLA2-induced pathology in cardiovascular disease in mouse model, in human aortic smooth muscle cells [ 25 ] and in type II alveolar epithelial cells exposed to cigarette smoke condensate [ 26 ].…”

Section: Structure and Function Of Cpla2mentioning

confidence: 99%

Dynamic Role of Phospholipases A2 in Health and Diseases in the Central Nervous System

Sun

Geng

Teng

et al. 2021

Cells

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Phospholipids are major components in the lipid bilayer of cell membranes. These molecules are comprised of two acyl or alkyl groups and different phospho-base groups linked to the glycerol backbone. Over the years, substantial interest has focused on metabolism of phospholipids by phospholipases and the role of their metabolic products in mediating cell functions. The high levels of polyunsaturated fatty acids (PUFA) in the central nervous system (CNS) have led to studies centered on phospholipases A2 (PLA2s), enzymes responsible for cleaving the acyl groups at the sn-2 position of the phospholipids and resulting in production of PUFA and lysophospholipids. Among the many subtypes of PLA2s, studies have centered on three major types of PLA2s, namely, the calcium-dependent cytosolic cPLA2, the calcium-independent iPLA2 and the secretory sPLA2. These PLA2s are different in their molecular structures, cellular localization and, thus, production of lipid mediators with diverse functions. In the past, studies on specific role of PLA2 on cells in the CNS are limited, partly because of the complex cellular make-up of the nervous tissue. However, understanding of the molecular actions of these PLA2s have improved with recent advances in techniques for separation and isolation of specific cell types in the brain tissue as well as development of sensitive molecular tools for analyses of proteins and lipids. A major goal here is to summarize recent studies on the characteristics and dynamic roles of the three major types of PLA2s and their oxidative products towards brain health and neurological disorders.

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Therapeutic potential of arachidonyl trifluromethyl ketone, a cytosolic phospholipaseA2 IVA specific inhibitor, in cigarette smoke condensate-induced pathological conditions in alveolar type I & II epithelial cells

Cited by 7 publications

References 32 publications

Multiscale Co‐reconstruction of Lung Architectures and Inhalable Materials Spatial Distribution

Multiscale Co‐reconstruction of Lung Architectures and Inhalable Materials Spatial Distribution

Thorium Alters Lung Surfactant Protein Expression in Alveolar Epithelial Cells: In Vitro and In Vivo Investigation

Dynamic Role of Phospholipases A2 in Health and Diseases in the Central Nervous System

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