PMID- 35832482
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 1664-042X (Print)
IS  - 1664-042X (Electronic)
IS  - 1664-042X (Linking)
VI  - 13
DP  - 2022
TI  - Modification of Fibronectin by Non-Enzymatic Glycation Impairs K(+) Channel 
      Function in Rat Cerebral Artery Smooth Muscle Cells.
PG  - 871968
LID - 10.3389/fphys.2022.871968 [doi]
LID - 871968
AB  - Fibronectin (FN) enhances K(+) channel activity by integrin-mediated mechanisms. 
      As vascular smooth muscle (VSM) K(+) channels mediate vasodilation, we 
      hypothesized that modification of fibronectin, via advanced non-enzymatic 
      glycation, would alter signaling of this extracellular matrix protein through 
      these channels. Bovine FN (1 mg/ml) was glycated (gFN) for 5 days using 
      methylglyoxal (50 mM), and albumin was similarly glycated as a non-matrix protein 
      control. VSM cells were isolated from rat cerebral arteries for measurement of 
      macroscopic K(+) channel activity using whole cell patch clamp methodology. 
      Pharmacological inhibitors, iberiotoxin (0.1 muM) and 4-aminopyridine (0.1 mM), 
      were used to identify contributions of large-conductance, Ca(2+)-activated, K(+) 
      channels and voltage-gated K(+) channels, respectively. Compared with baseline, 
      native FN enhanced whole cell K(+) current in a concentration-dependent manner, 
      whereas gFN inhibited basal current. Furthermore, native albumin did not enhance 
      basal K(+) current, but the glycated form (gAlb) caused inhibition. gFN was shown 
      to impair both the Kv and BK(Ca) components of total macroscopic K(+) current. 
      Anti-integrin alpha5 and beta1 antibodies attenuated the effects of both FN and gFN on 
      macroscopic K(+) current at +70 mV. Consistent with an action on BK(Ca) activity, 
      FN increased, whereas gFN decreased the frequency of spontaneous transient 
      outward current (STOCs). In contrast, gAlb inhibited whole cell K(+) current 
      predominantly through Kv, showing little effect on STOCs. A function-blocking, 
      anti-RAGE antibody partially reversed the inhibitory effects of gFN, suggesting 
      involvement of this receptor. Further, gFN caused production of reactive oxygen 
      species (ROS) by isolated VSMCs as revealed by the fluorescent indicator, DHE. 
      Evoked ROS production was attenuated by the RAGE blocking antibody. Collectively, 
      these studies identify ion channel-related mechanisms (integrin and ROS-mediated) 
      by which protein glycation may modify VSMC function.
CI  - Copyright (c) 2022 Yang, Nourian, Li, Sun, Zhang, Davis, Meininger, Wu, Braun and 
      Hill.
FAU - Yang, Yan
AU  - Yang Y
AD  - Dalton Cardiovascular Research Center, Columbia, MO, United States.
FAU - Nourian, Zahra
AU  - Nourian Z
AD  - Dalton Cardiovascular Research Center, Columbia, MO, United States.
FAU - Li, Min
AU  - Li M
AD  - Dalton Cardiovascular Research Center, Columbia, MO, United States.
FAU - Sun, Zhe
AU  - Sun Z
AD  - Dalton Cardiovascular Research Center, Columbia, MO, United States.
FAU - Zhang, Liping
AU  - Zhang L
AD  - Dalton Cardiovascular Research Center, Columbia, MO, United States.
AD  - Department of Medical Pharmacology and Physiology, University of Missouri, 
      Columbia, MO, United States.
AD  - Southwest Medical University, Luzhou, China.
AD  - Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, 
      Canada.
FAU - Davis, Michael J
AU  - Davis MJ
AD  - Dalton Cardiovascular Research Center, Columbia, MO, United States.
AD  - Department of Medical Pharmacology and Physiology, University of Missouri, 
      Columbia, MO, United States.
FAU - Meininger, Gerald A
AU  - Meininger GA
AD  - Dalton Cardiovascular Research Center, Columbia, MO, United States.
AD  - Department of Medical Pharmacology and Physiology, University of Missouri, 
      Columbia, MO, United States.
FAU - Wu, Jianbo
AU  - Wu J
AD  - Southwest Medical University, Luzhou, China.
FAU - Braun, Andrew P
AU  - Braun AP
AD  - Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, 
      Canada.
FAU - Hill, Michael A
AU  - Hill MA
AD  - Dalton Cardiovascular Research Center, Columbia, MO, United States.
AD  - Department of Medical Pharmacology and Physiology, University of Missouri, 
      Columbia, MO, United States.
LA  - eng
PT  - Journal Article
DEP - 20220627
PL  - Switzerland
TA  - Front Physiol
JT  - Frontiers in physiology
JID - 101549006
PMC - PMC9272009
OTO - NOTNLM
OT  - K+ channels
OT  - advanced glycation end-products (AGE)
OT  - extracellular matrix
OT  - fibronectin (FN)
OT  - protein modification
OT  - smooth muscle
OT  - vascular dysfunction and damage
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/07/15 06:00
MHDA- 2022/07/15 06:01
PMCR- 2022/06/27
CRDT- 2022/07/14 02:23
PHST- 2022/02/08 00:00 [received]
PHST- 2022/05/30 00:00 [accepted]
PHST- 2022/07/14 02:23 [entrez]
PHST- 2022/07/15 06:00 [pubmed]
PHST- 2022/07/15 06:01 [medline]
PHST- 2022/06/27 00:00 [pmc-release]
AID - 871968 [pii]
AID - 10.3389/fphys.2022.871968 [doi]
PST - epublish
SO  - Front Physiol. 2022 Jun 27;13:871968. doi: 10.3389/fphys.2022.871968. eCollection 
      2022.