Seeing lipids more deeply with mass spectrometry

Date:
March 10, 2022
Source:
Tokyo Medical and Dental University
Summary:
PRMC-MS allows enhanced profiling of phosphoinositide acyl variants
both in intracellular and extracellular environments.



FULL STORY ==========================================================================
The development of new scientific ways to see more deeply into the
building blocks of nature on a cellular level has led to the some of the greatest advances in medicine over the last century. Now, new research
into phosphoinositides, which are a family of membrane lipids essential
for many biological and pathological processes and which represent one
of the most functionally versatile membrane lipid families involved in
human health and disease, has seen further developments in the use of
mass spectrometry in continuing to push back the barriers leading to
new treatments for many diseases.


==========================================================================
In the past, due to various reasons related to their complexity and
their low intracellular concentrations, the profiling of these lipids
and the linking of a specific acyl variant to biological change has
been difficult. However, a new system called PRMC-MS (Phosphoinositide Regioisomer Measurement by Chiral column chromatography and Mass
Spectrometry) has now enabled the characterization of the dynamics of phosphoinositide acyl variants both in intracellular and extracellular environments.

Previous methods of measuring and profiling phosphoinositides have
produced results that cannot be easily applied to clinical or pathological samples from experimental animals. Even newer methods involving the
use of mass-spectrometry which have made advances in some areas still
reflect the problem of how to simultaneously quantify the acyl variants
of individual regioisomers in biological samples.

The PRMC-MS method now solves this problem and points the way to
an understanding of how these lipids influence cell functions. Using
PRMC-MS, it is now possible to simultaneously measure all eight classes
of phosphoinositides in a single sample. The highly sensitive nature
of PRMC-MS allows for the detection of tiny but important changes in intracellular phosphoinositide levels, yielding data that shows that
it can be applied to blood samples to track phosphoinositide signatures potentially related to disease states.

PRMC-MS enables the comprehensive analysis of phosphoinositide acyl
variants in various types of biological samples, including surgical
specimens, which can be used to throw a light on previously unrecognized disturbances of phosphoinositide fatty acyl profiles in cancerous
tissue and to monitor their extracellular mobilization. Further study
of the differing acyl variants and their conferring of protein binding properties could possibly also reveal how they activate a signaling
pathway that favors cancer cell growth and survival and emerge as
a target for cancer therapy. Thus, PRMC-MS may well illuminate the
role played by phosphoinositides in the pathogenesis of cancers and inflammatory diseases.

In addition, the use of PRMC-MS in the evaluation of phosphoinositide signatures at the acyl variant level in tissue and liquid biopsies may
reveal biomarkers suitable for a wide variety of clinical applications.

In the future, applications such as the above may greatly facilitate
drug development strategies based on the devising of a therapeutic agent
that pinpoints a specific pathogenic phosphoinositide acyl variant,
and thus open the way for much more accurate therapeutic methods and
cures for patients suffering from a range of diseases that have proven difficult in the past.


========================================================================== Story Source: Materials provided by
Tokyo_Medical_and_Dental_University. Note: Content may be edited for
style and length.


========================================================================== Journal Reference:
1. Shin Morioka, Hiroki Nakanishi, Toshiyoshi Yamamoto, Junya
Hasegawa, Emi
Tokuda, Tomoya Hikita, Tomoko Sakihara, Yuuki Kugii, Chitose
Oneyama, Masakazu Yamazaki, Akira Suzuki, Junko Sasaki, Takehiko
Sasaki. A mass spectrometric method for in-depth profiling of
phosphoinositide regioisomers and their disease-associated
regulation. Nature Communications, 2022; 13 (1) DOI:
10.1038/s41467-021-27648-z ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/03/220310114304.htm

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