Cardiomyocytes - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 206

The molecular chaperone, heat shock protein HSPb5, 30 abounds in the
myocardium. It may act in the assembly and remodeling of sarcomeres. Under
normal conditions, HSPb5 lodges in the cytosol; it is only slightly linked to the
cytoskeleton. During stress, it moves to the Z disc of the sarcomere and can interact
with actin, myosin, desmin, titin and vimentin, hence stabilizing sarcomeric and
cytoskeletal structures. Once phosphorylated by P38MAPK and MAPKAPK2 and
then translocated to mitochondria, it protects against acute metabolic stresses, such
as ischemia and reperfusion, as it also maintains mitochondrial integrity, hence
impeding H 2 O 2 -induced cytochrome-C release [ 360 ]. Chaperones HSPb5 and
HSP47 might play complementary roles in cross-bridging actin filaments in the
Z disc of the sarcomere.

5.3.1 Myofibrils

Each myofibril is made of arrays of parallel filaments. In the H zone, the thick and
thin filaments never overlap (Figs. 5.3 ).

30 A;k.a. heat shock protein-

B-crystallin. Chaperones
are aimed at protecting proteins from misfolding and aggregation. Most chaperones are stress
inducible. They belong to the HSP family. In addition to proper folding of newly synthesized
proteins, chaperones are also required during stress to assist in the maintenance of proteins struc-
ture and prevent aggregation. Oxidative stress and increase in intracellular calcium concentration
can indeed lead to protein unfolding and aggregation. In mammals, crystallins are divided into
α

β 5, 20-kDa heat shock-like protein, and α

-, β -, and γ -crystallins. Members of the α -and β -families are subdivided into acidic (e.g., α A-

crystallin, heat shock protein- β -4, or HSPb4) and basic (e.g., α B-crystallin or HSPb5) components.

(Heat shock protein- β 6, or α -crystallin-related HSPb6, is also called heat shock protein HSP20;

heat shock protein- β 1, or HSPb1, 27 or 28-kDa stress-responsive protein SRP27 (HSP25/27/28);

heat shock protein- β 2, or HSPb2, 27-kDa heat shock protein [HSP27]; heat shock protein- β 3,

or HSPb3, 17-kDa heat shock protein [HSP17]. Other -crystallin-related heat shock proteins

encompass cardiovascular HSPb7, or cvHSP, HSPb8, or small stress protein-like protein HSP22,
HSPb9, and HSPb10, or outer dense fiber of sperm tails ODF1, ODF2, and ODF27.)

α

B-Crystallin
interacts with numerous related small heat shock proteins (sHSP), such as HSPb1, HSPb6, and
HSPb8, to form multimers. α -Crystallins are not only constituents of the ocular lens with both
structural and functional homology with small heat shock proteins, but also reside in various types
of tissues, especially with a high concentration in the myocardium, particularly at Z discs and
intercalated discs. Whereas α A-crystallin is preferentially restricted to the lens, α B-crystallin is
widespread. α B-Crystallin is produced in the brain, lung, kidney, skeletal muscle and heart. Nodal
cells of the sinoatrial and atrioventricular nodes and His bundle contain a lower amount of α B-
crystallin than cardiomyocytes, whereas nodal cells of the left and right bundle branches possess a
greater quantity [ 359 ].

α