TABLE 1.

ROS-induced modifications of cardiac sarcomeric proteins

Protein	Modification type	Major target site	Functional effect	Ref.
Actin	Oxidation	Cys374	↓Myosin ATPase activity	11
			↓Actin filament sliding velocity	12
			↑F-actin depolymerization	13
			↓Tm-actin binding	10
			↓Maximum force	13
		Tyr	↓Contractile function	20, 22, 96
α-Actinin	Oxidation	Tyr	↓Longitudinal force transmission	21
Desmin	Oxidation	Cys	↓Proteasome degradation	18, 19
			↑Aggregate formation	18, 19
			↑Myofibrillar disarray	18, 19
		Tyr	↓Contractile function	22
MHC	Oxidation	Cys697/Cys707	↑Myosin inhibition	8, 10
			↓Maximum force	7, 9, 10
		Tyr	↓Contractile function	20
cMyBP-C	Oxidation	Cys, Tyr	↓Contractile function	9, 20
	Phosphorylation	Ser302 (PKA, PKCϵ, PKCδ, PKD)	↓Thin-thick filament interactions, ↑force generation	32, 39, 40
Titin	Oxidation	N2-B Cys	↓Extensibility	16
			↑Passive tension	16
	Phosphorylation	Ser469 (PKA, PKG)	↓Passive tension	41, 42
		Ser11878/Ser12022 (PKCα)	↑Passive tension	43
Tm	Oxidation	Cys190	↓Contractile function	11, 14
			↓Flexibility	13, 15
			↓Binding to actin	14
			↓Assembly of actin·Tm complexes	15
		Tyr	↓Contractile function	20, 22
cTnI	Phosphorylation	Ser23/Ser24 (PKA, PKC, PKG, PKD, p90RSK)	↑Ca2+ dissociation from TnC	23–32
			↓Ca2+ sensitivity
			↑Rate of relaxation
		Ser43/Ser45 (PKC)	↓Maximal force	33
		Thr144 (PKCβ, tyrosine-phosphorylated PKCδ, Mst1)	↑Myofilament Ca2+ sensitivity	28
		Thr32/Thr52/Thr130 (Mst1)	Altered conformation	71
		Ser151 (PAK-3)	↑Myofilament Ca2+ sensitivity	23
cTnT	Oxidation	Tyr	↓Contractile function	22
	Phosphorylation	Thr206 (PKC, Raf)	↓Maximal force	34, 36
			↓Myofilament Ca2+ sensitivity
		Thr197/Ser201 (PKC, ASK-1)	May exacerbate the effect of Thr206	34, 37
		Ser274/Thr287 (PKC)	May exacerbate the effect of Thr206	34, 36