Table 5.

GHK effects on antioxidant genes.

Up	Genes	Percent change in gene expression	Comments
1	TLE1	762	Inhibits the oxidative/inflammatory gene NF-κB [21].
2	SPRR2C	721	This proline-rich, antioxidant protein protects outer skin cells from oxidative damage from ROS. When the ROS level is low, the protein remains in the outer cell membrane but when the ROS level is high, the protein clusters around the cell's DNA to protect it [22, 23].
3	ITGB4	609	Upregulation of ITGB4 promotes wound repair ability and antioxidative ability [24].
4	APOM	403	Binds oxidized phospholipids and increases the antioxidant effect of HDL [25].
5	PON3	319	Absence of PON3 (paraoxonase 3) in mice resulted in increased rates of early fetal and neonatal death. Knockdown of PON3 in human cells reduced cell proliferation and total antioxidant capacity [26].
6	IL18BP	295	The protein encoded by this gene is an inhibitor of the proinflammatory cytokine IL18. IL18BP abolished IL18 induction of interferon-gamma (IFNgamma), IL8, and activation of NF-κB in vitro. Blocks neutrophil oxidase activity [27].
7	HEPH	217	Inhibits the conversion of Fe(2+) to Fe(3+). HEPH increases iron efflux, lowers cellular iron levels, suppresses reactive oxygen species production, and restores mitochondrial transmembrane potential [28].
8	FABP1	186	Reduces intracellular ROS level. Plays a significant role in reduction of oxidative stress [29, 30].
9	PON1	149	PON1 (paraoxonase 1) is a potent antioxidant and a major anti-atherosclerotic component of high-density lipoprotein [31].
10	MT3	142	Metallothioneins (MTs) display in vitro oxyradical scavenging capacity, suggesting that they may specifically neutralize hydroxyl radicals. Metallothioneins and metallothionein-like proteins isolated from mouse brain act as neuroprotective agents by scavenging superoxide radicals [32, 33].
11	PTGS2	120	Produces cyclooxygenase-II (COX-II) which has antioxidant activities [34].
12	NF-κB2	103	NF-κB, an oxidative/inflammatory protein, is involved in cellular responses to stimuli such as stress, cytokines, free radicals, ultraviolet irradiation, oxidized LDL, and bacterial or viral antigens [21].
13	NFE2L2	56	Nuclear respiratory factor 2 helps activate antioxidant responsive element regulated genes which contribute to the regulation of the cellular antioxidant defense systems [35].
14	PTGS1	50	Produces cyclooxygenase-I (COX-I) which has antioxidant activity [34].
Down	Genes	Percent change in gene expression	Comments
1	IL17A	−1018	This strongly suppressed cytokine can stimulate the expression of IL6 and cyclooxygenase-2 (PTGS2/COX-2), as well as enhancing the production of nitric oxide (NO). High levels of this cytokine are associated with several chronic inflammatory diseases including rheumatoid arthritis, psoriasis, and multiple sclerosis (NCBI GENE entry).
2	TNF	−115	GHK suppresses this prooxidant TNF gene which inhibits the antioxidant IL18 [36].