Hypotaurine

The Macrocallista nimbosa

Hypotaurine (2-aminoethanesulfinic acid), an intermediate in taurine biosynthesis from cysteine in astrocytes, is an endogenous inhibitory amino acid of the glycine receptor.

In Vitro:Hypotaurine and taurine are found to reside within the cytosolic compartment of the cell. The ratio of taurine to hypotaurine is approx 50:1. The cytosolic concentration of taurine is approx. 50 mM. The concentration of hypotaurine decreases by 80% when resting neutrophils are converted into actively respiring cells by exposure to opsonized zymosan[1]. Hypotaurine activates hypoxia signaling through the competitive inhibition of prolyl hydroxylase domain-2. This leads to the activation of hypoxia signaling as well as to the enhancement of glioma cell proliferation and invasion[2].

In Vivo:Hypotaurine has antinociceptive effects on thermal, mechanical, and chemical nociception in the spinal cord. In CCI rats, hypotaurine alleviates mechanical allodynia and thermal hyperalgesia. Intrathecal hypotaurine suppresses acute, inflammatory, and neuropathic pain. Hypotaurine may regulate nociceptive transmission physiologically by activating glycinergic neurons in the spinal cord[3].

References:
[1]. Green TR, et al. Antioxidant role and subcellular location of hypotaurine and taurine in human neutrophils. Biochim Biophys Acta. 1991 Jan 23;1073(1):91-7. https://www.ncbi.nlm.nih.gov/pubmed/1846756 [2]. Gao P, et al. Hypotaurine evokes a malignant phenotype in glioma through aberrant hypoxic signaling. Oncotarget. 2016 Mar 22;7(12):15200-14. [3]. Hara K, et al. Antinociceptive effect of intrathecal administration of hypotaurine in rat models of inflammatory and neuropathic pain. Amino Acids. 2012 Jul;43(1):397-404. Hara K, et al. Antinociceptive effect of intrathecal administration of hypotaurine in rat models of inflammatory and neuropathic pain. Amino Acids. 2012 Jul;43(1):397-404.

Protective effect of hypotaurine against oxidative stress-induced cytotoxicity in rat placental trophoblasts.[Pubmed:25801460]

Placenta. 2015 Jun;36(6):693-8.

INTRODUCTION: Hypotaurine is a precursor of taurine and an antioxidant, and is concentrated in fetal plasma compared to maternal plasma. Hypotaurine is significantly decreased in fetal plasma of ezrin (Vil2) knock-out mice, and fetuses show intrauterine growth retardation. The aim of this study was to characterize the mechanism through which cellular Hypotaurine level is maintained in placental trophoblasts, and the effect of Hypotaurine on oxidative stress induced by hydrogen peroxide (H2O2). METHODS: Hypotaurine transfer from extracellular fluid and antioxidant effect of Hypotaurine were analyzed in rat placental trophoblast TR-TBT 18d-1 cells. RESULTS: We found that Hypotaurine is concentrated into rat placental trophoblast TR-TBT 18d-1 cells, and the level of Hypotaurine was markedly reduced by culture in medium supplemented with dialyzed fetal bovine serum (FBS) instead of normal FBS. The Hypotaurine level recovered almost completely when Hypotaurine was added to the culture medium, indicating that intracellular Hypotaurine is predominantly supplied by transport across the plasma membrane from extracellular fluid rather than by biosynthesis. Hypotaurine showed a cytoprotective effect against H2O2-induced oxidative damage in TR-TBT 18d-1 cells. Hypotaurine treatment of TR-TBT 18d-1 cells increased antioxidant capacity against hydroxyl radical and peroxyl radical. The concentration of intracellular hydroxyl radical induced by H2O2 in TR-TBT 18d-1 cells was significantly reduced by Hypotaurine treatment. DISCUSSION: These results indicate that intracellular Hypotaurine is mainly supplied to placental trophoblasts by transfer from extracellular fluid across the plasma membrane, and may play a role in cell protection by scavenging reactive oxygen species.

Raffinose and hypotaurine improve the post-thawed Merino ram sperm parameters.[Pubmed:23644017]

Cryobiology. 2013 Aug;67(1):34-9.

The aim of this study was to determine the effects of raffinose and Hypotaurine on sperm parameters after the freeze-thawing of Merino ram sperm. Totally 40 ejaculates of five Merino ram were used in the study. Semen samples, which were diluted with a Tris-based extender containing 10mM raffinose, 5mM Hypotaurine, 5mM raffinose +2.5mM Hypotaurine (H+R) and no antioxidant (control), were cooled to 5 degrees C and frozen in 0.25 ml French straws and stored in liquid nitrogen. Frozen straws were then thawed individually at 37 degrees C for 25s in a water bath for evaluation. The addition of raffinose led to higher percentages of subjective and CASA motilities (47.5 +/- 12.2%, 46.3 +/- 13.6%) compared to controls (38.8 +/- 13.8%, 30.5 +/- 11.7%, P<0.05). For the CASA progressive motility, 5mM raffinose (20.12 +/- 8.82%) had increasing effect in comparison to control (10 +/- 7.94%, P<0.05) following the freeze-thawing process. Raffinose and Hypotaurine led to higher viability (40.8 +/- 4.68%, 40.8 +/- 4.7%), high sperm mitochondrial activity (29.5 +/- 5.4%, 27.3 +/- 4.9%) and acrosome integrity (50.8 +/- 8.1, 50.7 +/- 4.4) percentages, compared to control groups (31.5 +/- 3.5%, 9.5 +/- 8.2%, 42.8 +/- 7.3%, P<0.05). H+R group only led to high sperm mitochondrial activity when compared to control group. In the comet test, raffinose and Hypotaurine resulted in lower sperm with damaged DNA (6.2% and 3.9%) than that of control (9.1%), reducing the DNA damage. For TUNEL assay, The TUNEL-positive cell was distinguished by distinct nuclear staining. Raffinose and H+R groups resulted in lower sperm with TUNEL-positive cell (1.5 +/- 1.2% and 2.1 +/- 0.9%) than that of control (4.9 +/- 2.5%) (P<0.05). In conclusion, findings of this study showed that raffinose and Hypotaurine supplementation in semen extenders provided a better protection of sperm parameters against cryopreservation injury, in comparison to the control groups.

Antinociceptive effect of intrathecal administration of hypotaurine in rat models of inflammatory and neuropathic pain.[Pubmed:21971909]

Amino Acids. 2012 Jul;43(1):397-404.

Hypotaurine is an intermediate in taurine biosynthesis from cysteine in astrocytes. Although Hypotaurine functions as an antioxidant and organic osmolyte, its physiological role in the central nervous system remains unclear. This study used behavioral assessments to determine whether Hypotaurine influenced nociceptive transmission in acute, inflammatory, and neuropathic pain. The tail flick, paw pressure, and formalin tests were performed in male Sprague-Dawley rats to examine the effects of the intrathecal administration of Hypotaurine (100, 200, 400, 600 mug) on thermal, mechanical, and chemical nociception. Chronic constriction injury (CCI) to the sciatic nerve was induced in the rats, and the electronic von Frey test and plantar test were performed to assess the effects on neuropathic pain. To determine which neurotransmitter pathway(s) was involved in the action of Hypotaurine, in this study, we examined how the antagonists of spinal pain processing receptors altered the effect of 600 mug Hypotaurine. To explore whether Hypotaurine affected motor performance, the Rotarod test was conducted. Hypotaurine had antinociceptive effects on thermal, mechanical, and chemical nociception in the spinal cord. In CCI rats, Hypotaurine alleviated mechanical allodynia and thermal hyperalgesia. These effects were reversed completely by pretreatment with an intrathecal injection of strychnine, a glycine receptor antagonist. Conversely, Hypotaurine did not affect motor performance. This study demonstrated that intrathecal Hypotaurine suppressed acute, inflammatory, and neuropathic pain. Hypotaurine may regulate nociceptive transmission physiologically by activating glycinergic neurons in the spinal cord, and it is a promising candidate for treating various pain states.

Propargylglycine inhibits hypotaurine/taurine synthesis and elevates cystathionine and homocysteine concentrations in primary mouse hepatocytes.[Pubmed:25772816]

Amino Acids. 2015 Jun;47(6):1215-23.

Our investigation showed that hepatocytes isolated from cysteine dioxygenase knockout mice (Cdo1(-/-)) had lower levels of Hypotaurine and taurine than Cdo1 (+/+) hepatocytes. Interestingly, Hypotaurine accumulates in cultured wild-type hepatocytes. DL-propargylglycine (PPG, inhibitor of cystathionine gamma-lyase and H2S production) dramatically decreased both taurine and Hypotaurine levels in wild-type hepatocytes compared to untreated cells. Addition of 2 mM PPG resulted in the decrease of the intracellular taurine levels: from 10.25 +/- 5.00 observed in control, to 2.53 +/- 0.68 nmol/mg protein (24 h of culture) and from 17.06 +/- 9.40 to 2.43 +/- 0.26 nmol/mg protein (control vs. PPG; 48 h). Addition of PPG reduced also intracellular Hypotaurine levels: from 7.46 +/- 3.55 to 0.31 +/- 0.12 nmol/mg protein (control vs. PPG; 24 h) and from 4.54 +/- 3.20 to 0.42 +/- 0.11 nmol/mg protein (control vs. PPG; 48 h). The similar effects of PPG on Hypotaurine and taurine levels were observed in culture medium. PPG blocked Hypotaurine/taurine synthesis in wild-type hepatocytes, suggesting that it strongly inhibits cysteinesulfinate decarboxylase (pyridoxal 5'-phosphate-dependent enzyme) as well as cystathionine gamma-lyase. In the presence of PPG, intracellular and medium cystathionine levels for both wild-type and Cdo1 (-/-) cells were increased. Addition of homocysteine or methionine resulted in higher intracellular concentrations of homocysteine, which is a cosubstrate for cystathionine beta-synthase (CBS). It seems that PPG increases CBS-mediated desulfhydration by enhancing homocysteine levels in hepatocytes. There were no overall effects of PPG or genotype on intracellular or medium glutathione levels.

Reactivity of hypotaurine and cysteine sulfinic acid toward carbonate radical anion and nitrogen dioxide as explored by the peroxidase activity of Cu,Zn superoxide dismutase and by pulse radiolysis.[Pubmed:25156684]

Free Radic Res. 2014 Nov;48(11):1300-10.

Hypotaurine and cysteine sulfinic acid are known to be readily oxidized to the respective sulfonates, taurine and cysteic acid, by several oxidative agents that may be present in biological systems. In this work, the relevance of both the carbonate anion and nitrogen dioxide radicals in the oxidation of Hypotaurine and cysteine sulfinic acid has been explored by the peroxidase activity of Cu,Zn superoxide dismutase (SOD) and by pulse radiolysis. The extent of sulfinate oxidation induced by the system SOD/H2O2 in the presence of bicarbonate (CO3(*-) generation), or nitrite ((*)NO2 generation) has been evaluated. Hypotaurine is efficiently oxidized by the carbonate radical anion generated by the peroxidase activity of Cu,Zn SOD. Pulse radiolysis studies have shown that the carbonate radical anion reacts with Hypotaurine more rapidly (k = 1.1 x 10(9) M(-1)s(-1)) than nitrogen dioxide (k = 1.6 x 10(7) M(-1)s(-1)). Regarding cysteine sulfinic acid, it is less reactive with the carbonate radical anion (k = 5.5 x 10(7) M(-1)s(-1)) than Hypotaurine. It has also been observed that the one-electron transfer oxidation of both sulfinates by the radicals is accompanied by the generation of transient sulfonyl radicals (RSO2(*)). Considering that the carbonate radical anion could be formed in vivo at high level from bicarbonate, this radical can be included in the oxidants capable of performing the last metabolic step of taurine biosynthesis. Moreover, the protective effect exerted by Hypotaurine and cysteine sulfinate on the carbonate radical anion-mediated tyrosine dimerization indicates that both sulfinates have scavenging activity towards the carbonate radical anion. However, the formation of transient reactive intermediates during sulfinate oxidation by carbonate anion and nitrogen dioxide radical may at the same time promote oxidative reactions.

Inhibitory actions of taurocyamine, hypotaurine, homotaurine, taurine and GABA on spike discharges of Purkinje cells, and localization of sensitive sites, in guinea pig cerebellar slices.[Pubmed:7214140]

Brain Res. 1981 Feb 16;206(2):371-86.

The effects of the possible metabolites of taurine--taurocyamine and Hypotaurine--and of homotaurine on spike discharge frequency of guinea pig cerebellar Purkinje cells were investigated in comparison with taurine and GABA. Taurocyamine, Hypotaurine and homotaurine all dose-dependently suppressed the spike frequency with potencies relative to taurine (ED50 = 1.0 mM) of 6, 0.5 and 500, respectively. Both picrotoxin and strychnine competitively blocked the inhibition by all the substances tested, except for the non-competitive antagonism by picrotoxin on taurocyamine. The sites sensitive to taurocyamine and Hypotaurine were situated primarily in the dendritic region of the cerebellar molecular layer, while those to homotaurine were primarily near the Purkinje cell soma. The onset of the inhibitory action of taurine and related sulfur-containing substances was found to be slower than that of GABA.

Hypotaurine (2-aminoethanesulfinic acid), an intermediate in taurine biosynthesis from cysteine in astrocytes, is an endogenous inhibitory amino acid of the glycine receptor.

Hypotaurine,300-84-5,2-Aminoethanesulfinic acid,Natural Products,Glycine Receptors, buy Hypotaurine , Hypotaurine supplier , purchase Hypotaurine , Hypotaurine cost , Hypotaurine manufacturer , order Hypotaurine , high purity Hypotaurine