Merck
  • Incorporation of Oxidized Phenylalanine Derivatives into Insulin Signaling Relevant Proteins May Link Oxidative Stress to Signaling Conditions Underlying Chronic Insulin Resistance.

Incorporation of Oxidized Phenylalanine Derivatives into Insulin Signaling Relevant Proteins May Link Oxidative Stress to Signaling Conditions Underlying Chronic Insulin Resistance.

Biomedicines (2022-05-29)
Judit Mohás-Cseh, Gergő Attila Molnár, Marianna Pap, Boglárka Laczy, Tibor Vas, Melinda Kertész, Krisztina Németh, Csaba Hetényi, Orsolya Csikós, Gábor K Tóth, Attila Reményi, István Wittmann
摘要

A link between oxidative stress and insulin resistance has been suggested. Hydroxyl free radicals are known to be able to convert phenylalanine (Phe) into the non-physiological tyrosine isoforms ortho- and meta-tyrosine (o-Tyr, m-Tyr). The aim of our study was to examine the role of o-Tyr and m-Tyr in the development of insulin resistance. We found that insulin-induced uptake of glucose was blunted in cultures of 3T3-L1 grown on media containing o- or m-Tyr. We show that these modified amino acids are incorporated into cellular proteins. We focused on insulin receptor substrate 1 (IRS-1), which plays a role in insulin signaling. The activating phosphorylation of IRS-1 was increased by insulin, the effect of which was abolished in cells grown in m-Tyr or o-Tyr media. We found that phosphorylation of m- or o-Tyr containing IRS-1 segments by insulin receptor (IR) kinase was greatly reduced, PTP-1B phosphatase was incapable of dephosphorylating phosphorylated m- or o-Tyr IRS-1 peptides, and the SH2 domains of phosphoinositide 3-kinase (PI3K) bound the o-Tyr IRS-1 peptides with greatly reduced affinity. According to our data, m- or o-Tyr incorporation into IRS-1 modifies its protein-protein interactions with regulating enzymes and effectors, thus IRS-1 eventually loses its capacity to play its role in insulin signaling, leading to insulin resistance.

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磷酸酶抑制剂混合物2, aqueous solution (dark coloration may develop upon storage, which does not affect the activity)
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L-酪氨酸, from non-animal source, meets EP, USP testing specifications, suitable for cell culture, 99.0-101.0%
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磷酸酶抑制剂混合物 1, DMSO solution
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L-Meta-tyrosine, ≥98% (HPLC)
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Anti-phospho-Insulin Receptor Substrate-1 (pTyr612) antibody produced in rabbit, affinity isolated antibody, buffered aqueous glycerol solution
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Anti-Insulin Receptor Substrate 1 (IRS-1) antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution