Analysis of Lipid Contents in Human Trabecular Meshwork Cells by Multiple Reaction Monitoring (MRM) Profiling Lipidomics

Wang, Ting; Pattabiraman, Padmanabhan P

doi:10.1007/978-1-0716-2966-6_24

Cited by 2 publications

(2 citation statements)

References 16 publications

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“…The lipid extraction was performed as per the Bligh and Dyer protocol 65 . Lipidomics and data analysis were processed as published earlier 41,66 . In addition, pathway enrichment analysis was also performed to identify the most relevant pathways associated with the identified metabolites using a web‐based analysis module (http://metaboanalyst.ca), which is based on Globaltest.…”

Section: Methodsmentioning

confidence: 99%

“…65 Lipidomics and data analysis were processed as published earlier. 41,66 In addition, pathway enrichment analysis was also performed to identify the most relevant pathways associated with the identified metabolites using a web-based analysis module (http://metab oanal yst.ca), which is based on Globaltest. Through pathway analysis, eight metabolic pathways related to the identified metabolites (n = 274) were mapped.…”

Section: Cellular Lipid Extraction and Multiple Reaction Monitoring (...mentioning

confidence: 99%

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Identification of the novel role of sterol regulatory element binding proteins (SREBPs) in mechanotransduction and intraocular pressure regulation

Wang,

Soundararajan,

Rabinowitz

et al. 2023

The FASEB Journal

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Trabecular meshwork (TM) cells are contractile and mechanosensitive, and they aid in maintaining intraocular pressure (IOP) homeostasis. Lipids are attributed to modulating TM contractility, with poor mechanistic understanding. In this study using human TM cells, we identify the mechanosensing role of the transcription factors sterol regulatory element binding proteins (SREBPs) involved in lipogenesis. By constitutively activating SREBPs and pharmacologically inactivating SREBPs, we have mechanistically deciphered the attributes of SREBPs in regulating the contractile properties of TM. The pharmacological inhibition of SREBPs by fatostatin and molecular inactivation of SREBPs ex vivo and in vivo, respectively, results in significant IOP lowering. As a proof of concept, fatostatin significantly decreased the SREBPs responsive genes and enzymes involved in lipogenic pathways as well as the levels of the phospholipid, cholesterol, and triglyceride. Further, we show that fatostatin mitigated actin polymerization machinery and stabilization, and decreased ECM synthesis and secretion. We thus postulate that lowering lipogenesis in the TM outflow pathway can hold the key to lowering IOP by modifying the TM biomechanics.

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Section: Methodsmentioning

confidence: 99%

Section: Cellular Lipid Extraction and Multiple Reaction Monitoring (...mentioning

confidence: 99%

Identification of the novel role of sterol regulatory element binding proteins (SREBPs) in mechanotransduction and intraocular pressure regulation

Wang,

Soundararajan,

Rabinowitz

et al. 2023

The FASEB Journal

Self Cite

View full text Add to dashboard Cite

show abstract

Identification of the novel role of sterol regulatory element binding proteins (SREBPs) in mechanotransduction and intraocular pressure regulation

Wang

Soundararajan

Rabinowitz

et al. 2023

Preprint

View full text Add to dashboard Cite

Trabecular meshwork (TM) cells are highly contractile and mechanosensitive to aid in maintaining intraocular pressure (IOP) homeostasis. Lipids are attributed to modulating the TM contractility with poor mechanistic understanding. In this study using human TM cells, we identify the mechanosensing role of the transcription factors sterol regulatory element binding proteins (SREBPs) involved in lipogenesis. By constitutively activating SREBPs and pharmacologically inactivating SREBPs, we have mechanistically deciphered the attributes of SREBPs in regulating the contractile properties of TM. The pharmacological inhibition of SREBPs by fatostatin and molecular inactivation of SREBPs ex vivo and in vivo respectively results in significant IOP lowering. As a proof of concept, fatostatin significantly decreased the SREBPs responsive genes and enzymes involved in lipogenic pathways as well as the levels of the phospholipid, cholesterol, and triglyceride. Further, we show that fatostatin mitigated actin polymerization machinery and stabilization, and decreased ECM synthesis and secretion. We thus postulate that lowering lipogenesis in the TM outflow pathway can hold key to lowering IOP by modifying the TM biomechanics.

show abstract

Analysis of Lipid Contents in Human Trabecular Meshwork Cells by Multiple Reaction Monitoring (MRM) Profiling Lipidomics

Cited by 2 publications

References 16 publications

Identification of the novel role of sterol regulatory element binding proteins (SREBPs) in mechanotransduction and intraocular pressure regulation

Identification of the novel role of sterol regulatory element binding proteins (SREBPs) in mechanotransduction and intraocular pressure regulation

Identification of the novel role of sterol regulatory element binding proteins (SREBPs) in mechanotransduction and intraocular pressure regulation

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