scholarly journals Zinc exocytosis is sensitive to myosin light chain kinase inhibition in mouse and human eggs

2020 ◽  
Vol 26 (4) ◽  
pp. 228-239 ◽  
Author(s):  
Hoi Chang Lee ◽  
Maxwell E Edmonds ◽  
Francesca E Duncan ◽  
Thomas V O’Halloran ◽  
Teresa K Woodruff
Keyword(s):  
Embryo Development ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Kinase Inhibitor ◽  
Early Embryo ◽  
Egg Activation ◽  
Cortical Granules ◽  
Preimplantation Embryo Development ◽  
Egg Maturation

Abstract Zinc dynamics are essential for oocyte meiotic maturation, egg activation, and preimplantation embryo development. During fertilisation and egg activation, the egg releases billions of zinc atoms (Zn2+) in an exocytotic event termed the ‘zinc spark’. We hypothesised that this zinc transport and exocytosis is dependent upon the intracellular trafficking of cortical granules (CG) which requires myosin-actin-dependent motors. Treatment of mature mouse and human eggs with ML-7, a myosin light chain kinase inhibitor (MLCK), resulted in an 80% reduction in zinc spark intensity compared to untreated controls when activated with ionomycin. Moreover, CG migration towards the plasma membrane was significantly decreased in ML-7-treated eggs compared with controls when activated parthenogenetically with ionomycin. In sperm-induced fertilisation via intracytoplasmic sperm injection (ICSI), ML-7-treated mouse eggs exhibited decreased labile zinc intensity and cortical CG staining. Collectively, these data demonstrate that ML-7 treatment impairs zinc release from both murine and human eggs after activation, demonstrating that zinc exocytosis requires myosin light chain kinase activity. Further, these results provide additional support that zinc is likely stored and released from CGs. These data underscore the importance of intracellular zinc trafficking as a crucial component of egg maturation necessary for egg activation and early embryo development.

Myosin Light Chain Kinase Inhibitor Inhibits Dextran Sulfate Sodium-Induced Colitis in Mice

2012 ◽  
Vol 58 (1) ◽  
pp. 107-114 ◽  
Author(s):  
Xiaochang Liu ◽  
Jianming Xu ◽  
Qiao Mei ◽  
Liang Han ◽  
Jian Huang
Keyword(s):  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Kinase Inhibitor

scholarly journals Total Synthesis of MS-444, a Myosin Light Chain Kinase Inhibitor

1997 ◽  
Vol 50 (3) ◽  
pp. 289-290 ◽  
Author(s):  
KUNIAKI TATSUTA ◽  
TAKUJI YOSHIMOTO ◽  
HIROKI GUNJI
Keyword(s):  
Total Synthesis ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Kinase Inhibitor

scholarly journals Participation of protein kinases in complement C5b-9-induced shedding of platelet plasma membrane vesicles

Blood ◽  
1991 ◽  
Vol 78 (11) ◽  
pp. 2880-2886
Author(s):  
T Wiedmer ◽  
PJ Sims
Keyword(s):  
Plasma Membrane ◽  
Protein Kinase ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Kinase Inhibitor ◽  
Complement Proteins ◽  
Cellular Events ◽  
Microparticle Formation ◽  
Terminal Complement

The formation of membrane microparticles through vesiculation of the platelet plasma membrane is known to provide catalytic surface for several enzyme complexes of the coagulation system, and to underlie the procoagulant responses elicited with platelet activation. This induced shedding of vesicles from the plasma membrane is most prominent when platelets are activated by the terminal complement proteins, C5b-9, by a Ca2+ ionophore, or by the combination of thrombin plus collagen. Although shown to require elevated [Ca2+], the cellular events that initiate plasma membrane evagination and fusion to form the shed vesicles remain unresolved. To gain additional insight into the cellular events that regulate membrane microparticle formation, we have examined how this process is influenced by the activity of cellular protein kinases. Cytoplasmic [Ca2+] of gel-filtered platelets was increased by membrane assembly of the terminal complement proteins C5b- 9 in the presence of selective inhibitors of protein kinase or phosphatase reactions, and resulting microparticle formation was quantitated by fluorescence-gated flow cytometry. Pre-equilibration of the phosphatase inhibitor vanadate into the platelet cytosol increased microparticle formation by as much as 40%, suggesting that vesiculation of the platelet plasma membrane is influenced by the state of phosphorylation of a cellular constituent. By contrast to the stimulatory effects of vanadate, microparticle formation was partially inhibited in platelets treated with the protein kinase inhibitor sphingosine, the myosin light chain kinase inhibitor ML-7, the calmodulin-antagonist W-7, and under conditions of elevated cytosolic concentration of cyclic adenosine monophosphate. These results indicate that complement-induced platelet microparticle formation is influenced by one or more protein kinase(s) as well as by calmodulin, and suggest a role for the platelet myosin light chain kinase or another Ca(2+)- pluscalmodulin-regulated membrane component.

52 A NOVEL MYOSIN LIGHT CHAIN KINASE INHIBITOR, PIK, PROTECTS FROM LIPOPOLYSACCHARIDE-INDUCED ACUTE LUNG INJURY.

2007 ◽  
Vol 55 (2) ◽  
pp. S357.1-S357
Author(s):  
T. Mirzapoiazova ◽  
S. Sammani ◽  
L. Moreno ◽  
S. M. Dudek ◽  
J. R. Turner ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Kinase Inhibitor

A NOVEL MYOSIN LIGHT CHAIN KINASE INHIBITOR, PIK, PROTECTS FROM LIPOPOLYSACCHARIDE-INDUCED ACUTE LUNG INJURY.

2007 ◽  
Vol 55 (2) ◽  
pp. S357
Author(s):  
T. Mirzapoiazova ◽  
S. Sammani ◽  
L. Moreno ◽  
S. M. Dudek ◽  
J. R. Turner ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Kinase Inhibitor
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