. 2019 Aug 16;8(8):315. doi: 10.3390/antiox8080315

Table 1.

Summary of S-glutathionylation activation (green) or inhibition (red) effects on major molecular players in endothelial cell (EC) function and their physiological consequences.

Protein Name	Protein Type	Glutathionylated Cysteine(s)	Direct Effect(s) on Protein	Physiological Effect(s) in ECs	Reference(s)
4.1. Epigenetics regulators
Histone H3	Nucleosomal	C110	Not confirmed	Regulation of gene expression via modulating chromatin structure	[13,14]
Sirtuin1	Histone deacetylase	C67 C268 C623	Inhibition of enzymatic activity	Apoptosis - Senescence	[15,16,17]
4.2. Transcription factors
p65	Transcription factor	Unknown	Inhibition of nuclear translocation	Angiogenesis & cell survival	[18]
p50		C62	Inhibition of DNA-binding activity	Angiogenesis & cell survival	[19]
c-jun		C269	Inhibition of DNA-binding activity	Unknown	[20,21]
p53		C124 C141 C182	Inhibition of DNA-binding and protein dimerization	Angiogenesis & cell survival (supposed)	[22]
HIF-1a		C520	Protein stabilization	Angiogenesis & ischemic revascularisation	[23,24]
STAT3		C328 C542	Inhibition of phosphorylation and activity	Anti-angiogenesis and reduced inflammation	[25,26,27,28]
STAT1		C324 C492	Protein activation	Unknown	[28]
Keap1	Nrf2 inhibitor	C434	Inhibition of Nrf2 binding	Antioxidant and anti-inflammatory response via Nrf2 signalling	[29,30]
IKKb	Kinase	C179	Inhibition of kinase activity	Angiogenesis & neovascularisation	[31]
5. Kinases & phosphatases
LMW PTP	Phosphatase	Unknown	Inhibition of activity	Cell migration and angiogenesis	[32]
PTP1B	Phosphatase	C215		Not confirmed	[33,34]
Rac1	Small Rho GTPase	C81 C157		Altered actin structure and barrier function	[35,36]
Rac2	Small Rho GTPase	C157	Increased GTP-binding activity	Unknown	[36,37]
Ras	GTPase	C118	Not confirmed	Unknown	[36,38,39]
PKA	Kinase	C199	Inhibition of activity	Alteration of barrier function and blood pressure regulation (supposed)	[40,41]
PKB		Unknown			[40,42,43]
MEKK1		C1238			[40,44]
PKC		Unknown			[40,45]
6. RONS production
p47 phox	NADPH oxidase	C98 C111 C196	Enhanced protein function	Sustained superoxide production Endothelial dysfunction (supposed)	[46]
Complex I	NADH-ubiquinone oxidoreductase	Unknown	Enhanced protein function		[47]
eNOS	Oxide synthase	C689 C908	Protein uncoupling	Sustained superoxide production Impaired vasodilation and endothelial dysfunction	[48,49,50,51,52]
7. Calcium-dependent channels
IP3R	Ca²⁺ channel	Unknown (C34 C42 C65?)	Protein activation	Increased [Ca²⁺]_i Regulation of Ca²⁺ homeostasis	[53,54,55]
PMCA	Ca²⁺ ATPase pump	Unknown	Protein inhibition	Increased [Ca²⁺]_i Regulation of Ca²⁺ homeostasis	[56]
SERCA2b	Ca²⁺ ATPase pump	C674	Protein activation	Increased Ca²⁺ uptake in ER stores Cell migration and angiogenesis	[57,58,59,60,61,62]
STIM1	Ca²⁺ sensor	C56	Protein oligomerization	Increased [Ca]_i via Orai1 activation Mitochondrial dysfunction	[63]
8. Apoptosis and autophagy
Fas	Death receptor	C294	Enhanced activity	Cell death	[64]
Caspase-3	Protease	C45 (p12) C135 (p17)	Inhibition of proteolytic activity	Cell survival	[65,66]
Caspase-8	Protease	Unknown	Inhibition of proteolytic activity	Cell survival	[67]
Beclin-1	Autophagy-related protein	Unknown	Upregulation of protein activity	Not confirmed	[68]
9. Cell structure and dynamics
ProMMPs	Metalloprotease	PRCGVPD motif on inhibitory domain	Activation	Angiogenesis and vascular permeability	[69]
ICAM-1	Adhesion receptor	Unknown	Protein degradation	Cell junction disassembly	[70]
Actin	Cytoskeletal	C374	Inhibition of polymerization	Inhibition of cell motility	[71,72,73]
Microtubules	Cytoskeletal	Unknown	Inhibition of polymerization	Cell growth arrest and apoptosis	[74,75]