2012

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BIOMEDICAL SCIENCES

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Further Research
needed to
understand the
role of H2S as a
biological mediator
and therapeutic
potential

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Vol. 1 No. 1:1

doi: 10.3823/1000

Arun Kumar, Utpal Kumar Biswas

In contrast to its role as poison, hydrogen sulfide (H2S) is now considered as the third
gaso transmitter after nitric oxide (NO) and carbon monoxide (CO) [1,2,3]. Though
it was first reported in 1982 that they are produced in mammalian tissues, but it is
only now emerged as a mediator of important physiologic functions in humans [4].
In the central nervous system (CNS), H2S functions not only as a neuro-modulator,
but also as a neuro-protectant against oxidative stress[5]. In the cardiovascular system, H2S relaxes vascular smooth muscles by the activation of K ATPchannels and
inhibits smooth muscle cell proliferation via the mitogen-activated protein kinase
signaling pathway [6]. These effects are important for maintaining normal blood
pressure and preventing vessel structural remodeling, and identifies [7, 8, 9, 10].
H2S as an important factor in controlling the progression of some vascular diseases,
such as hypertension. Hydrogen sulfide (H2S) also has cardio protective effects
in ischemic myocardium, septicemia and endotoxin shock [13, 14, 15, 16]. Recent
studies have demonstrated a new mechanism to explain the motor effect of H2S on
the rat detrusor muscle, which is through the activation of the capsaicin-sensitive
primary neuron [17]. H2S is synthesized endogenously in various mammalian tissues
by two pyridoxal 5 phosphate dependent enzymes responsible for metabolizing Lcysteine: cystathionine beta synthase (CBS, EC 4.2.1.22) and cystathionine gamma
lyase (CSE, EC 4.4.1.1). The substrate of CBS and CSE, L-cysteine, can be derived
from alimentary sources or can be liberated from endogenous proteins [18]. It can
also be synthesized endogenously from L-methionine through the trans-sulfuration
pathway, with homocysteine being an intermediate in the process[19]. Compared
to other gaseous mediators, H2S is rapidly eliminated by several mechanisms thus
keeping its levels within safe limits. H2S can be oxidized to sulfate, methylated,
conjugated with glutathione or methemoglobin, and reacted with metalloproteins
and disulfide-containing proteins [20]. Oxidation of H2S is presumably the primary
mechanism of elimination. In vitro experiments have shown that H2S generated
from sulfide salts (Na2S and NaSH) inhibits cellular damage and intracellular protein oxidation induced by HOCl, ONOO- and NO. Its sulfide salts (NaSH) is also
reported to scavenge and/or degrade lipid peroxides and inhibit the expression and
activity of NAD(P)H oxidase [21]. Increased hepatic glutathione (GSH) synthesis and
decreased lipid peroxidation are also observed with Na2S treatment in a murine
hepatic ischemiareperfusion injury model [22]. In neuronal cells, NaSH shown to
inhibit cell death induced by -amyloid and MPP+ mediated, at least in part, via
antioxidant effects, and up regulated intracellular GSH synthesis [23].
It is worth noting that the whole tissueand circulating concentrations of H2S have
recently been reported to be negligible amount. The physiologic concentrations
varies from organ to organ, and values have been reported to be spanning from
< 1 nmol/g of tissue to >100 nmol/g of tissue [24]. These vast differences in levels
have raised several quests about H2S as a mediator. Perhaps most importantly,
it is suggested that H2S is degraded instantly once it accomplishes its function.
Triggered to these spanning levels of H2S it could be hypothesized that the actions of H2S are localized, occurring largely at the autocrine or paracrine level

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of signaling[25,26]. Evidence is accumulating to demonstrate

that inhibitors of H2S production or therapeutic H2S donor
compounds exert significant effects in various animal models
of inflammation, reperfusion injury and circulatory shock [27,
28]. H2S can also induce a reversible state of hypothermia
and suspended-animation-like state in rodents [29]. Over the
couple of years, though many scientific reports have come
out on H2S, related to its biological role and therapeutic potential [30, 31, 32, 33], still a number of questions need to be
addressed. Further research needed to understand the role
of H2S as a biological mediator and its therapeutic potential.
H2S, even being familiar and widely known for over a century
but it is only now it is being evaluated for its physiological
roles, can be a trigger for the current researches in biomedical sciences.

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2012
BIOMEDICAL SCIENCES

Vol. 1 No. 1:1

doi: 10.3823/1000

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BIOMEDICAL SCIENCES

Vol. 1 No. 1:1

doi: 10.3823/1000

31. Shin Chet Chuah, Philip K. Moore, and Yi Zhun Zh. S-allylcysteine
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