Improved Wound Healing of Airway Epithelial Cells Is Mediated by Cold Atmospheric Plasma: A Time Course-Related Proteome Analysis

Table 1

Assignment of protein clusters to short-term and/or long-term responses.

Response	Cluster	Protein spots with highest/lowest -score	Molecular & cellular functions	Top Tox	Overall conclusions/remarks
Short-term increased	1	TCPA, 2AAA, CATB, GDIA, NUCB1, PDIA3 (↑)	Cell death	Mechanism of gene regulation by peroxisome proliferators via PPAR alpha	(i) Induction of peroxisome production to overcome oxidative stress; (ii) Activation of transcription factors (PPARs) involved in anti-inflammatory functions; (iii) Induction of Nrf2 and their target genes to deal with oxidative stress; (iv) Prevention of apoptosis; (v) Some cell death events in damaged cells; (vi) Posttranslational modifications caused by oxidative stress; (vii) Beginning of protein folding and repair; (viii) Protection of cell integrity and cell homeostasis; (ix) ER stress response; (x) Maintenance of microtubule dynamics; (xi) Control of proteins through Ca^2+ binding; (xii) Stop of cell growth and proliferation; (xiii) Protein synthesis stop, elimination; (→) Present enzymes have to function
			Posttranslational modifications	PPAR alpha/RXR alpha activation
			Protein folding	Nrf2-mediated oxidative stress response
Short-term increased	2	PDIA1 (P4HB), GRP78, GLU2B, RCN1, PDIA3, CH60 (↑)	Posttranslational modifications	Decrease permeability transition of mitochondria and mitochondrial membrane
			Protein folding	Hypoxia-inducible factor signalling
			Cellular function and maintenance	Nrf2-mediated oxidative stress response
Short-term increased	10	CALM, HSPB1, PDIA3, PSB7, RD23B, RCN2, PRS4 (↑)	Cellular growth and proliferation	Liver necrosis/cell death
			Posttranslational modification	Decrease permeability transition of mitochondria and mitochondrial membrane
			Protein folding	Oxidative stress
Short-term decreased	5	SET, BASP, SPEE, HS90A, FSTL1, EF2, CBX1 (↓)	Cellular growth and proliferation	Nrf2-mediated oxidative stress response
			Posttranslational modification	Liver necrosis/cell death
			Protein folding	Decrease permeability transition of mitochondria and mitochondrial membrane
Short-term decreased	6	SSRD, CBX3, NPM, C1QBP, ERP29, ANXA2 (↓)	Protein degradation	Nrf2-mediated oxidative stress response
			Cell death	Decrease permeability transition of mitochondria and mitochondrial membrane
			Gene expression	Oxidative stress
Short-term decreased	7	HNRL2, HNRPC, HS90A, SGTA, NP1L1, CNDP2 (↓)	Cellular growth and proliferation	Nrf2-mediated oxidative stress response
			Cell death	Cell cycle: G2/M DNA damage checkpoint regulation
			Posttranslational modification	Oxidative stress
Short-term decreased	9	PPT1, ANXA3, VINC, SCMC1, TPM1, K1C17 (↓)	Cellular growth and proliferation	Hypoxia-inducible factor signalling
			Cellular assembly and organization	Nrf2-mediated oxidative stress response
			Cell death	Aryl hydrocarbon receptor signalling
Long-term increased	3	HYOU1, ATPB, GRP78, SYG, PDIA3, SF3B2, PSME1 (↑)	Posttranslational modifications	PPAR alpha/RXR alpha activation	(i) ER stress response; (ii) Refolding of misfolded proteins replenishment by new synthesis; (iii) Stop of mitosis to ensure the repair of oxidative or DNA damages; (iv) Some Nrf2-related proteins are downregulated; (v) Characterized more by cell metabolism, e.g., AA metabolism
			Protein folding	Mechanism of gene regulation by peroxisome proliferators via PPAR alpha
			Amino acid metabolism	Cell cycle: G2/M DNA damage checkpoint regulation
Long-term decreased	4	U2AF2, CALD1, GSTO1, CTNA1, PNPO, RFC2 (↓)	Posttranslational modifications	Nrf2-mediated oxidative stress response
			Protein folding	Aryl hydrocarbon receptor signalling
			Cell morphology	Hypoxia-inducible factor signalling
Long-term decreased	8	EGF1, GELS, SODC, SF3B2, GANAB, PARK7 (↓)	Cellular growth and proliferation	Nrf2-mediated oxidative stress response
			Cell death	Increase transmembrane potential of mitochondria and mitochondrial membrane
			Cellular function and maintenance	Aryl hydrocarbon receptor signalling

Relevant cellular and molecular functions and Top Tox responses (ranks 1-3) revealed by IPA analyses are mentioned. Reasoned functions are indicated as well as some proteins with highest or lowest -score.