Biomedical Engineering Reference
In-Depth Information
43 is involved in the activation of the PKB-GSK3
β
axis by PI3K
c1γ
possibly via
its interaction with the G
β
subunit of G protein, but not via mitochondrial ROS
production.
5.2.3.5
Myoglobin
Myoglobin is an iron- and oxygen-binding protein of myocytes that functions
in oxygen transport and storage. In addition, as a reductase, deoxygenated myo-
globin generates nitric oxide from circulating nitrite. On the other hand, oxymyo-
globin acts as a dioxygenase to convert NO into nitrates [
350
]. Low concentration
of nitrite ions (NO
2
) cause vasodilation and suppression of mitochondrial activity,
thereby reducing generation of reactive oxygen species, especially after ischemia-
reperfusion events. Owing to nitrite reductase, nitrite ions generate nitric oxide, a
vasorelaxant that decreases cardiomyocyte contractility and cardiac frequency by
repressing the electron transport chain in mitochondria.
5.2.3.6
Mechanotransduction
Mitochondrial depolarization and K
+
accumulation in the mitochondrial matrix by
activated ATP- or Ca
2
+
-dependent K
+
channels and inhibited H
+
-K
+
exchanger
strongly increase contractile force in rat ventriculomyocytes [
351
]. Change in
the mitochondrial ionic balance causes mitochondrial swelling that can compress
the myofibrillar and nuclear compartments of cardiomyocytes that are sensitive
to extracellular mechanical stimuli. A relatively small increase in mitochondrial
volume can cause a relatively large reduction in sarcomeric lattice spacing in the
absence of strong stretch of cardiomyocytes and concomitant increase in passive
force [
351
].
When myosin and actin filaments are closer, both myofilament Ca
2
+
sensitivity
and maximal Ca
2
+
-induced tension increase. In addition, mechanical stresses
applied on the nucleus can influence both the DNA accessibility for gene tran-
scription and the nucleocytoplasmic transport of molecules. Therefore, generated
internal pressure that affects morphological and functional properties of organelles
contributes to the regulation of cell functioning [
351
].
5.2.3.7
Cardioprotection
Cardioprotection relies on [
352
]: (1) activation of numerous cardioprotective ki-
nases, such as extracellular signal-regulated protein kinase, phosphatidylinositol
3-kinase, and protein kinase B; (2) translocation to the mitochondria of kinases
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