S-nitrosylation and the interaction between H2S
and NO
For S-nitrosylation two mechanisms have been proposed. NO was initially
thought only to diffuse after being produced by NO synthase (NOS) to the
target proteins to S-nitrosylate them (Lancaster, 2017). However, it has
been demonstrated that S-nitrosylation proceeds by clusters of enzymes
which generate NO, synthesize S-nitrosylated proteins, and
transnitrosylate it (Seth et al., 2018). Signaling by
H2S, H2Sn and NO as well
as S-sulfuration and S-nitrosylation must have both diffusion mediated-
and enzyme oriented- mechanisms for regulating the activity of targets.
Synergistic effect of H2S with NO on vascular relaxation
led to the identification of two mechanisms (Hosoki et al., 1997). One
is that the chemical interaction between H2S and NO
produces H2Sn, nitosothiol, thionitrous
acid (HSNO), and nitrosopersulfide (HSSNO) that have the relaxation
effect greater than each parental molecule (Nagai et al., 2006; Whiteman
et al, 2006; Oosumi et al., 2010; Filipovic et al., 2012; Ebenhardt et
al, 2014; Stubbert et al., 2014; Cortese-Krott et al., 2015; Moustafa
and Habara, 2016; Miyamoto et al., 2017; See also Kimura, 2020). Another
mechanism is that H2S and NO mutually regulate their
synthesizing enzymes (Zhao et al., 2001; Minamishima et al., 2009; Kondo
et al., 2013; King et al., 2014; Kimura, 2016). For chemical interaction
between H2S and NO, both molecules should diffuse to
interact with each other.
After the identification of EDRF as NO, there appeared a discrepancy.
EDRF hyperpolarizes the membrane of vascular smooth muscle, while NO has
little hyperpolarizing effect. Based on this observation it has been
suggested that EDRF contains an additional factor, endothelium-derived
hyperpolarizing factor (EDHF) (Chen et al., 1988). Because
H2S activates KATP channels and
hyperpolarizes the membrane potential, it has been proposed as a
potential EDHF (Hosoki et al., 1997; Zhuo et al., 2001; Mustafa et al.,
2011). Another possibility is H2Sn,
which are produced by the chemical interaction of H2S
with NO and activate protein kinase G1α (PKG1α) to relax vasculature,
are also potent substances to activate KATP channels by
S-sulfurating the active cysteine residue (Nagai et al., 2006; Whiteman
et al, 2006; Oosumi et al., 2010; Mustafa et al., 2011; Filipovic et
al., 2012; Ebenhardt et al, 2014; Stubbert et al., 2014; Cortese-Krott
et al., 2015; Moustafa and Habara, 2016; Miyamoto et al., 2017; See also
Kimura, 2020).