FATTY ACID REGULATION OF KEPATINOCYTE DIFFERENTIATION

Project: Research project

Project Details

Description

The overall objectives of the study are to determine whether essential
fatty acids play a role in the process of keratinocyte differentiation.
Preliminary evidence suggests that one essential fatty acid, linoleic acid,
may act as a regulator of differentiated function. The current proposal
seeks to understand the role of this polyunsaturated fatty acid in
epidermal biology. The metabolic fate of the fatty acid, which cannot be
biosynthesized and therefore must be exogenously supplied, will be traced.
Incorporation of radiolabeled linoleic acid into all lipid classes will be
examined by chromatographic analysis of cellular extracts, using TLC, GLC
and HPLC methodologies. In this way we will be able to determine which
lipid class may be the critical one to focus further studies on. The levels and distribution of linoleic acid in differentiating and
non-differentiating keratinocyte cultures will be determined and correlated
with known markers of differentiation. These include quantification of
squame formation and nuclear dissolution, PAGE analysis of keratins, and
assays of cell-associated plasminogen activator and transglutaminase
activities. In a parallel approach, keratinocytes will be enriched in
linoleic acid and examined for evidence of enhance differentiation. Lipids
will be extracted from these cells to determine if there is preferential
sequestration of linoleic acid in any particular lipid class. Finally, we will selectively block the metabolic pathways of eicosanoid
synthesis in linoleate-enriched keratinocytes to determine whether the
regulatory effect of linoleic acid is mediated by its prostaglandin or
leukotriene metabolites. These studies will help elucidate the role of linoleic acid in the
keratinocyte differentiative process and clarify the mechanism by which
this regulation is achieved.
StatusFinished
Effective start/end date7/1/836/30/88

Funding

  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

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