Redox States of Protein Cysteines in Pathways of Protein Turnover and Cytoskeleton Dynamics Are Changed with Aging and Reversed by Slc7a11 Restoration in Mouse Lung Fibroblasts

Table 1

Ingenuity Pathway Analysis (IPA) that indicated proteins whose redox states were restored by the Slc7a11 overexpression were enriched in pathways of protein turnover and cytoskeleton signaling. The top 3 most significant enriched pathways were protein synthesis pathway, protein ubiquitin-proteasome-mediated degradation pathway, and actin cytoskeleton signaling/integrin-linked kinase (ILK) signaling. Some proteins contained more than 1 redox-sensitive Cys residue. Some Cys residues became more oxidized with aging while others became more reduced.

Related IPA pathway	Change of redox state	Protein	Description	Redox-sensitive Cys	Abundance (old/young)	Redox state (old/young)
Protein synthesis pathway (EIF2 signaling)	Oxidized	EIF3C	Eukaryotic translation initiation factor 3 subunit C	GTTEEICQIYLR	0.74	2.86
		EIF4E	Eukaryotic translation initiation factor 4E	IAIWTTECENR	0.67	2.22
		RPL3	Ribosomal protein L3	VACIGAWHPAR	0.81	3.54
		RPL9	Ribosomal protein L9	TGVACSVSQAQK	N/A	4.76
		RPL11	Ribosomal protein L11	IAVHCTVR	0.71	2.22
		RPS2	Ribosomal protein S2	GCTATLGNFAK	0.76	2.17
		RPS6	Ribosomal protein S6	LNISFPATGCQK	0.67	3.19
	Reduced	ACTB	Actin beta	LCYVALDFEQEMATAASSSSLEK	N/A	0.31
		EIF2S3	Eukaryotic translation initiation factor 2 subunit gamma	IVLTNPVCTEVGEK	0.96	0.45
Actin cytoskeleton signaling/ILK signaling	Oxidized	ACTN4	Actinin alpha 4	ACLISLGYDVENDR	1.43	2.15
		ACTR3	ARP3 actin-related protein 3 homolog	YSYVCPDLVK	1.28	2.18
		FLNA	Filamin A	SNFTVDCSK	N/A	2.45
				CSGPGLSPGMVR	N/A	3.86
		MYH9	Myosin heavy chain 9	KQELEEICHDLEAR	1.82	2.53
		TLN1	Talin 1	QVAASTAQLLVACK	1.06	2.20
				CVSCLPGQR	1.06	2.34
				VVAPTISSPVCQEQLVEAGR	1.06	3.40
				AGALQCSPSDVYTK	1.06	2.58
		FLNB	Filamin B	IAGPGLSSCVR	1.36	2.17
				ACIPQSFTVDSSK	1.36	3.94
		PPP2CA	Protein phosphatase 2 catalytic subunit alpha	AHQLVMEGYNWCHDR	0.66	2.26
				QITQVYGFYDECLR	0.66	2.68
	Reduced	ACTB	Actin beta	LCYVALDFEQEMATAASSSSLEK	N/A	0.31
		GNG12	G protein subunit gamma 12	ASADLMSYCEEHAR	N/A	0.94
		IQGAP1	IQ motif containing GTPase activating protein 1	FFQVACDVPELQDK	1.54	0.21
		FLNC	Filamin C	DGSCGVSYVVQEPGDYEVSIK	N/A	0.22
Protein degradation pathway (proteasome-mediated)	Oxidized	PSMA6	Proteasome subunit alpha 6	YGYEIPVDMLCK	0.85	1.71
		PSMD9	Proteasome 26S subunit, non-ATPase 9	GIGMNEPLVDCEGYPR	0.73	1.98
		PSMD11	Proteasome 26S subunit, non-ATPase 11	TTANAIYCPPK	0.72	3.26
		PSMD13	Proteasome 26S subunit, non-ATPase 13	SSDEAVILCK	0.75	3.56
		SKP1	S-phase kinase-associated protein 1	GLLDVTCK	0.66	1.96
	Reduced	HSPA9	Heat shock protein family A (Hsp70) member 9	CELSSSVQTDINLPYLTMDASGPK	0.58	0.48
		PSMB1	Proteasome subunit beta 1	ICIVTK	0.80	0.57
		USO1	USO1 vesicle transport factor	SQLCSQSLEITR	N/A	0.39