期刊
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY, INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
卷 320, 期 1, 页码 R1-R18出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00212.2020
关键词
confocal colocalization; epoxomicin; fetal carotid arteries; myosin light-chain kinase; organ culture; ubiquitination
类别
资金
- National Institutes of Health [HD083132, HL135786, NS-076945]
- Loma Linda University School of Medicine
- National Science Foundation through the Major Research Instrumentation program of the Division of Biological Infrastructure [0923559]
Chronic hypoxia followed by hypoxic culture induced translocation of MLCK among at least three subcellular fractions, potentially affecting contractility in fetal arteries.
Changes in vascular contractility are among the most important physiological effects of acute and chronic fetal hypoxia. Given the essential role of myosin light-chain kinase (MLCK) in smooth muscle contractility and its heterogeneous distribution, this study explores the hypothesis that subcellular changes in MLCK distribution contribute to hypoxic modulation of fetal carotid artery contractility. Relative to common carotid arteries from normoxic term fetal lambs (FN), carotids from fetal lambs gestated at high altitude (3,802 m) (FH) exhibited depressed contractility without changes in MLCK mRNA or protein abundance. Patterns of confocal colocalization of MLCK with a-actin and 20-kDa regulatory myosin light chain (MLC20) enabled calculation of subcellular MLCK fractions: 1) colocalized with the contractile apparatus, 2) colocalized with a-actin distant from the contractile apparatus, and 3) not colocalized with a-actin. Chronic hypoxia did not affect MLCK abundance in the contractile fraction, despite a concurrent decrease in contractility. Organ culture for 72 h under 1% O2 decreased total MLCK abundance in FN and FH carotid arteries, but decreased the contractile MLCK abundance only in FH carotid arteries. Correspondingly, culture under 1% O2 depressed contractility more in FH than FN carotid arteries. In addition, hypoxia appeared to attenuate ubiquitin-independent proteasomal degradation of MLCK, as reported for other proteins. In aggregate, these results demonstrate that the combination of chronic hypoxia followed by hypoxic culture can induce MLCK translocation among at least three subcellular fractions with possible influences on contractility, indicating that changes in MLCK distribution are a significant component of fetal vascular responses to hypoxia.
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