Myosin light chain kinase steady‐state kinetics: comparison of smooth muscle myosin II and nonmuscle myosin IIB as substrates

Alcala, Diego B.; Haldeman, Brian D.; Brizendine, Richard K.; Krenc, Agata K.; Baker, Josh E.; Rock, Ronald S.; Cremo, Christine R.

doi:10.1002/cbf.3209

Cited by 9 publications

(8 citation statements)

References 56 publications

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“…There are reports showing that NM RLC phosphorylation may be catalyzed by several kinases, including ROCK, ZIP kinase (ZIPK), and MLCK (Holzapfel et al, 1983;Cande and Ezzell, 1986;Goeckeler and Wysolmerski, 1995;Connell and Helfman, 2006;Vicente-Manzanares et al, 2009;Alcala et al, 2016). We found that MLCK inhibition significantly attenuated NM RLC phosphorylation as well as NM RLC-mediated force tension.…”

Section: Discussionmentioning

confidence: 55%

Distinct Roles of Smooth Muscle and Non-muscle Myosin Light Chain-Mediated Smooth Muscle Contraction

et al. 2020

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Both smooth muscle (SM) and non-muscle (NM) myosin II are expressed in hollow organs such as the bladder and uterus, but their respective roles in contraction and corresponding physiological functions remain to be determined. In this report, we assessed their roles by analyzing mice deficient of Myl9, a gene encoding the SM myosin regulatory light chain (SM RLC). We find that global Myl9-deficient bladders contracted with an apparent sustained phase, despite no initial phase. This sustained contraction was mediated by NM myosin RLC (NM RLC) phosphorylation by myosin light chain kinase (MLCK). NM myosin II was expressed abundantly in the uterus and young mice bladders, of which the force was accordingly sensitive to NM myosin inhibition. Our findings reveal distinct roles of SM RLC and NM RLC in SM contraction.

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Section: Discussionmentioning

confidence: 55%

Distinct Roles of Smooth Muscle and Non-muscle Myosin Light Chain-Mediated Smooth Muscle Contraction

et al. 2020

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“…During the early stages of smooth muscle differentiation, NM-MHC (also referred to as SMemb) is the first isoform of myosin heavy chain to be expressed (25,38). As vascular maturation proceeds, NM-MHC is gradually replaced by SM-MHC, which has approximately twice the contractile efficiency as reflected by the higher rate of its phosphorylation by myosin light chain kinase (2). Correspondingly, changes in contractile phenotype can involve simultaneous changes in the colocalization of both SM-MHC and NM-MHC with ␣Actin, particularly in immature arteries.…”

Section: Resultsmentioning

confidence: 99%

Prenatal metyrapone treatment modulates neonatal cerebrovascular structure, function, and vulnerability to mild hypoxic-ischemic injury

Franco

Durrant

Carreon

et al. 2020

American Journal of Physiology-Regulatory, Integrative and Comp

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This study explored the hypothesis that late gestational reduction of corticosteroids transforms the cerebrovasculature and modulates postnatal vulnerability to mild hypoxic-ischemic (HI) injury. Four groups of Sprague-Dawley neonates were studied: 1) Sham-Control, 2) Sham-MET, 3) HI-Control, and 4) HI-MET. Metyrapone (MET), a corticosteroid synthesis inhibitor, was administered via drinking water from gestational day 11 to term. In Shams, MET administration 1) decreased reactivity of the hypothalamic-pituitary-adrenal (HPA) axis to surgical trauma in postnatal day 9 (P9) pups by 37%, 2) promoted cerebrovascular contractile differentiation in middle cerebral arteries (MCAs), 3) decreased compliance ≤46% and increased depolarization-induced calcium mobilization in MCAs by 28%, 4) mildly increased hemispheric cerebral edema by 5%, decreased neuronal degeneration by 66%, and increased astroglial and microglial activation by 10- and 4-fold, respectively, and 5) increased righting reflex times by 29%. Regarding HI, metyrapone-induced fetal transformation 1) diminished reactivity of the HPA axis to HI-induced stress in P9/P10 pups, 2) enhanced HI-induced contractile dedifferentiation in MCAs, 3) lessened the effects of HI on MCA compliance and calcium mobilization, 4) decreased HI-induced neuronal injury but unmasked regional HI-induced depression of microglial activation, and 5) attenuated the negative effects of HI on open-field exploration but enhanced the detrimental effects of HI on negative geotaxis responses by 79%. Overall, corticosteroids during gestation appear essential for normal cerebrovascular development and glial quiescence but induce persistent changes that in neonates manifest beneficially as preservation of postischemic contractile differentiation but detrimentally as worsened ischemic cerebrovascular compliance, increased ischemic neuronal injury, and compromised neurobehavior.

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“…Expression of NM-MHC decreases with vascular maturation [ 32 , 34 ]. SM-MHC becomes the predominant isoform and reflects a more mature, contractile-efficient phenotype with approximately twice the contractile efficiency as NM-MHC [ 43 ]. In relation to smooth muscle phenotype, a rightward shift in pixel distributions (e.g., decreased Low-Low and increased Low-High values) for colocalization of αActin with MHC, suggested contractile differentiation.…”

Section: Resultsmentioning

confidence: 99%

Maternal Undernutrition Modulates Neonatal Rat Cerebrovascular Structure, Function, and Vulnerability to Mild Hypoxic-Ischemic Injury via Corticosteroid-Dependent and -Independent Mechanisms

Franco

Durrant

Doan

et al. 2021

IJMS

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The present study explored the hypothesis that an adverse intrauterine environment caused by maternal undernutrition (MUN) acted through corticosteroid-dependent and -independent mechanisms to program lasting functional changes in the neonatal cerebrovasculature and vulnerability to mild hypoxic-ischemic (HI) injury. From day 10 of gestation until term, MUN and MUN-metyrapone (MUN-MET) group rats consumed a diet restricted to 50% of calories consumed by a pair-fed control; and on gestational day 11 through term, MUN-MET groups received drinking water containing MET (0.5 mg/mL), a corticosteroid synthesis inhibitor. P9/P10 pups underwent unilateral carotid ligation followed 24 h later by 1.5 h exposure to 8% oxygen (HI treatment). An ELISA quantified MUN-, MET-, and HI-induced changes in circulating levels of corticosterone. In P11/P12 pups, MUN programming promoted contractile differentiation in cerebrovascular smooth muscle as determined by confocal microscopy, modulated calcium-dependent contractility as revealed by cerebral artery myography, enhanced vasogenic edema formation as indicated by T2 MRI, and worsened neurobehavior MUN unmasked HI-induced improvements in open-field locomotion and in edema resolution, alterations in calcium-dependent contractility and promotion of contractile differentiation. Overall, MUN imposed multiple interdependent effects on cerebrovascular smooth muscle differentiation, contractility, edema formation, flow-metabolism coupling and neurobehavior through pathways that both required, and were independent of, gestational corticosteroids. In light of growing global patterns of food insecurity, the present study emphasizes that infants born from undernourished mothers may experience greater risk for developing neonatal cerebral edema and sensorimotor impairments possibly through programmed changes in neonatal cerebrovascular function.

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Myosin light chain kinase steady‐state kinetics: comparison of smooth muscle myosin II and nonmuscle myosin IIB as substrates

Cited by 9 publications

References 56 publications

Distinct Roles of Smooth Muscle and Non-muscle Myosin Light Chain-Mediated Smooth Muscle Contraction

Distinct Roles of Smooth Muscle and Non-muscle Myosin Light Chain-Mediated Smooth Muscle Contraction

Prenatal metyrapone treatment modulates neonatal cerebrovascular structure, function, and vulnerability to mild hypoxic-ischemic injury

Maternal Undernutrition Modulates Neonatal Rat Cerebrovascular Structure, Function, and Vulnerability to Mild Hypoxic-Ischemic Injury via Corticosteroid-Dependent and -Independent Mechanisms

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