Improvement of diabetes-induced spinal cord axon injury with taurine via nerve growth factor-dependent Akt/mTOR pathway.

Diabetic neuropathy (DN) is a common neurological complication caused by diabetes mellitus (DM). Axonal degeneration is generally accepted to be the major pathological change in peripheral DN. Taurine has been evidenced to be neuroprotective in various aspects, but its effect on spinal cord axon injury (SCAI) in DN remains barely reported. This study showed that taurine significantly ameliorated axonal damage of spinal cord (SC), based on morphological and functional analyses, in a rat model of DN induced by streptozotocin (STZ). Taurine was also found to induce neurite outgrowth in cultured cerebral cortex neurons with high glucose exposure. Moreover, taurine up-regulated the expression of nerve growth factor (NGF) and neurite outgrowth relative protein GAP-43 in rat DN model and cultured cortical neurons/VSC4.1 cells. Besides, taurine increased the activating phosphorylation signals of TrkA, Akt, and mTOR. Mechanistically, the neuroprotection by taurine was related to the NGF-pAKT-mTOR axis, because either NGF-neutralizing antibody or Akt or mTOR inhibitors was found to attenuate its beneficial effects. Together, our results demonstrated that taurine promotes spinal cord axon repair in a model of SCAI in STZ-induced diabetic rats, mechanistically associating with the NGF-dependent activation of Akt/mTOR pathway.

Non-pharmacological interventions for preventing emergence delirium in children under general anesthesia: A scoping review.

PROBLEM: The phenomenon of emergence delirium in pediatric patients undergoing general anesthesia has garnered increasing attention in the academic community. While formal non-pharmaceutical interventions have demonstrated efficacy in mitigating this phenomenon, the diversity of intervention types and their varying degrees of effectiveness necessitate further discussion. A scoping review was conducted to identify and explicate the categorization, content elements, and outcomes measures of non-pharmacological interventions utilized to forestall the onset of emergence delirium in children undergoing general anesthesia. ELIGIBILITY CRITERIA: This review was conducted in accordance with the Arksey and O'Malley's methodology framework and PRISMA-ScR. It encompassed experimental and quasi-experimental studies that involved any non-pharmacological interventions during the perioperative period to prevent emergence delirium in children aged 0 to 18 years undergoing general anesthesia for elective surgery. SAMPLE: Thirty-two articles met the inclusion criteria, of which 29 were randomized controlled trials. The total sample size of the population was 4633. RESULTS: The scoping review revealed 10 non-pharmacological interventions, that included distraction intervention, visual preconditioning, virtual reality, parental participation, maternal voice, light drinking, acupuncture, auditory stimulation, monochromic light and breathing training. Emergence delirium, preoperative anxiety, and postoperative pain were the primary outcomes, and four assessment instruments were employed to measure the extent and incidence of emergence delirium. CONCLUSION: Numerous non-pharmacological interventions have been employed to prevent emergence delirium. Nevertheless, the effectiveness of some interventions is not yet evident. IMPLICATIONS: The utilization of visual preconditioning and distraction interventions appears to be an emerging area of interest.

Kallikrein-related peptidase 10 predicts prognosis and mediates tumor immunomodulation in colorectal cancer.

The incidence and mortality rates of colorectal cancer (CRC) have significantly increased in recent years. It has been shown that early diagnosis of CRC improves the five-year survival of patients compared to late diagnosis, as patients with stage I disease have a five-year survival rate as high as 90 %. Through bioinformatics analysis, we identified Kallikrein 10 (KLK10), a member of the Kallikrein family, as a reliable predictor of CRC progression, particularly in patients with early-stage CRC. Furthermore, single-cell analysis revealed that KLK10 was highly expressed in tumor and partial immune cells. Analysis of the biological functions of KLK10 using the Kyoto encyclopedia of genes and genomes and gene ontology indicated that KLK10 plays a role in the proliferation and differentiation of cancer cells, along with the maintenance of tumor function and immune regulation, explicitly by T cells and macrophages. EdU cell proliferation staining, plate clone formation assay, and cell scratch assay demonstrated that KLK10 inhibition by siRNA affected the proliferation and migration of CRC cells. Cell cycle detection by flow cytometry demonstrated that KLK10 inhibition led to cell cycle arrest in the G1 phase. In addition, the proportion of M1 and M2 macrophages in 45 tumor specimens was analyzed by immunohistochemistry, the proportion of CD4+ T cells and CD8+ T cells in plasma was identified by flow cytometry, and their correlation with KLK10 was analyzed. The effects of KLK10 on T cells and macrophages were verified in independent cell experiments. The results revealed that KLK10 also activates CD4+ T cells, mediating M2-type macrophage polarization.

Curcumin attenuates Cr (VI)-induced cell growth and migration by targeting autophagy-dependent reprogrammed metabolism.

Hexavalent chromium [Cr (VI)] is a well-established carcinogen. Cr (VI)-treated cells are phenotypically characterized by aberrant levels of growth and migration. Curcumin, a polyphenolic compound from the plant turmeric, has been found to possess antiproliferation, anti-inflammation, and antioxidant properties. In this study, the effect of curcumin on Cr (VI)-induced cell survival and migration and the underlying mechanism were investigated. Cell viability assay on A549 and human embryonic lung fibroblast cells showed that curcumin at the concentration of 10 µM could significantly attenuate Cr (VI)-induced viability in both cell lines. Following Western blot assay and metabolomics assays, cotreatment with curcumin and Cr (VI) resulted in the suppression of Cr (VI)-induced glycolysis-, autophagy-, and migration-related proteins. Meanwhile, curcumin increased Cr (VI)-reduced oxidative phosphorylation (OXPHOS)-related proteins, COXIV and ND1. Moreover, curcumin suppressed Cr (VI)-induced mitochondrial dysfunction, mitochondrial mass decrease, and mitochondrial membrane potential loss. Treatment with curcumin for 24 h significantly attenuated pcATG4B-induced autophagy and the subsequent expression of glucose transporter 1, hexokinase II, and pyruvate kinase M2. Wound healing and transwell assay demonstrated that curcumin reduced Cr (VI)-induced cell migration. Taken together, these results showed that curcumin was able to attenuate Cr (VI)-induced cell viability and migration by targeting autophagy-dependent reprogrammed metabolism from OXPHOS to glycolysis.

The Role of SUMO E3 Ligases in Signaling Pathway of Cancer Cells.

Small ubiquitin-like modifier (SUMO)ylation is a reversible post-translational modification that plays a crucial role in numerous aspects of cell physiology, including cell cycle regulation, DNA damage repair, and protein trafficking and turnover, which are of importance for cell homeostasis. Mechanistically, SUMOylation is a sequential multi-enzymatic process where SUMO E3 ligases recruit substrates and accelerate the transfer of SUMO onto targets, modulating their interactions, localization, activity, or stability. Accumulating evidence highlights the critical role of dysregulated SUMO E3 ligases in processes associated with the occurrence and development of cancers. In the present review, we summarize the SUMO E3 ligases, in particular, the novel ones recently identified, and discuss their regulatory roles in cancer pathogenesis.

Taurine ameliorates axonal damage in sciatic nerve of diabetic rats and high glucose exposed DRG neuron by PI3K/Akt/mTOR-dependent pathway.

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes and axonopathy is its main pathological feature. Previous studies suggested an advantage of taurine against diabetes. However, there are few reports which study the effect of taurine against axonopathy. In this study, we confirmed that taurine significantly decreased blood glucose level, mitigated insulin resistance and improved dysfunctional nerve conduction in diabetic rats. Taurine corrected damaged axonal morphology of sciatic nerve in diabetic rats and induced axon outgrowth of Dorsal root ganglion (DRG) neurons exposed to high glucose. Taurine up-regulated phosphorylation levels of PI3K, Akt, and mTOR in sciatic nerve of diabetic rats and DRG neurons exposed to high glucose. However, Akt and mTOR inhibitors (MK-2206 and Rapamycin) blocked the effect of taurine on improving axonal damage. These results indicate that taurine ameliorates axonal damage in sciatic nerve of diabetic rats by activating PI3K/Akt/mTOR signal pathway. Our findings provide taurine as a potential candidate for axonopathy and a new evidence for elucidating protective mechanism of taurine on DPN.

NLRP3 inflammasome blocked the glycolytic pathway via targeting to PKLR in arsenic-induced hepatic insulin resistance.

Arsenic exposure is related to insulin resistance (IR). However, the underlying mechanism is still uncertain. NOD-like receptors containing pyrin domain 3 (NLRP3) inflammasome is a key driving factor of IR. We found that NaAsO2 caused hepatic IR, activated NLRP3 inflammasome, and inhibited glycolysis pathway in vivo. We also found that tricarboxylic acid cycle (TCA cycle) was inhibited, and the content of hepatic lactate was upregulated with the treatment of arsenic. Consistent with these findings, we found that NLRP3 inflammasome and glycolysis were involved in the development of IR in L-02 cells. Besides, inhibiting NLRP3 inflammasome upregulated aerobic glycolysis and inhibited anaerobic glycolysis. Moreover, we demonstrated that NLRP3 inflammasome could bind to pyruvate kinase, liver and RBC (PKLR). Simultaneously, insulin signaling rather than NLRP3 inflammasome activation was altered by overexpressing PKLR. In summary, after treatment with NaAsO2, NLRP3 inflammasome blocked the glycolytic pathway via binding to PKLR, which in turn caused hepatic IR. This study shed new light on the molecular mechanism underlying arsenic-induced IR.

The crosstalk between mitochondrial dysfunction and endoplasmic reticulum stress promoted ATF4-mediated mitophagy induced by hexavalent chromium.

Chromium (Cr) compounds are markedly toxic and carcinogenic. Previously, we found that Cr (VI) induced autophagy in A549 cells. Here, the effect of mitochondrial dysfunction and endoplasmic reticulum (ER) stress on inducing mitophagy was investigated in both A549 and H1299 cells. Exposure to Cr (VI) for 6 h significantly enhanced reactive oxygen species (ROS) production and reduced mitochondrial membrane potential (MMP). Transmission electron microscopy showed that Cr (VI) induced mitochondrial morphological changes, such as, mitochondrial swelling and vacuolization. The elevated expression of GRP78 and p-PERK suggested that Cr (VI) resulted in ER stress. Both mitochondrial dysfunction and ER stress played an important role in Cr (VI)-induced mitophagy, as the mitochondrial function inhibitor, carbonyl cyanide 3-chlorophenylhydrazone (CCCP) induced PINK1 and PARK2 and increased the expression of GRP78 and p-PERK while the levels of Cr (VI)-induced PINK1, PARK2, LC3-II were reduced after ER stress inhibitor, phenylbutyric acid (4PBA) pretreatment. When A549 cells were treated with CCCP and 4-PBA simultaneously, CCCP-induced expressions of PINK1, PARK2 and LC3-II decreased significantly compared with that of only CCCP-treated cells, indicating that there was a crosstalk between mitochondria and ER in inducing mitophagy. Additionally, the crosstalk between mitochondrial dysfunction and ER stress modulated the expression of Cr (VI)-induced ATF4, which resulted in mitophagy. Collectively, our data demonstrated that Cr (VI)-induced mitophagy mediated by ATF4 via the crosstalk between ER stress and mitochondrial dysfunction.

Effects of Mycobacterium tuberculosis Rv1096 on mycobacterial cell division and modulation on macrophages.

Mycobacterium tuberculosis is capable of escaping the clearance of immune system mainly due to its complex constituents of cell wall. Certain studies show that glycoproteins are involved in immune evasion and act as virulence factors. Peptidoglycan deacetylase Rv1096 is a member of mannosylated proteins. Previously, we reported Rv1096 protein contributed to the resistance of Mycobacterium smegmatis (M. smegmatis) to lysozyme, but more characterization of this protein is required where further intracellular function is unknown. Here, Rv1096 was heterologously over-expressed in the fast-growing and nonpathogenic M. smegmatis (named as M. smegmatis/Rv1096). We observed the morphological alterations in M. smegmatis/Rv1096 including an elongated rod-like shape and increased amounts of Z-rings, which implied that Rv1096 facilitated the cell growth and division. Moreover, a series of assays concerning the interaction between M. smegmatis/Rv1096 and host were carried out. The results showed that M. smegmatis/Rv1096 evaded the killing of macrophages due to the inhibition of phagosome-lysosome fusion, nicotinamide adenine dinucleotide phosphate oxidase activity and reactive oxygen species production. The secretion of interleukin-12 and tumor necrosis factor-α was also impaired by Rv1096. In addition, five putative interaction partners of Rv1096 were identified, which possibly cooperated with Rv1096 in cell division and immune regulation. These results suggested that Rv1096 had effects on mycobacterial division and might act as a virulence factor to mediate the immune evasion in macrophage during mycobacterial infection.

Taurine inhibits neuron apoptosis in hippocampus of diabetic rats and high glucose exposed HT-22 cells via the NGF-Akt/Bad pathway.

Type 2 Diabetes causes learning and memory deficits that might be mediated by hippocampus neuron apoptosis. Studies found that taurine might improve cognitive deficits under diabetic condition because of its ability to prevent hippocampus neuron apoptosis. However, the effect and mechanism is not clear. In this study, we explore the effect and mechanism of taurine on inhibiting hippocampus neuron apoptosis. Sixty male Sprague-Dawley rats were randomly divided into control, T2D, taurine treatment (giving 0.5%, 1%, and 2% taurine in drinking water) groups. Streptozotocin was used to establish the diabetes model. HT-22 cell (hippocampus neurons line) was used for in vitro experiments. Morris Water Maze test was used to check the learning and memory ability, TUNEL assay was used to measure apoptosis and nerve growth factor (NGF); Akt/Bad pathway relevant protein was detected by western blot. Taurine improved learning and memory ability and significantly decreased apoptosis of the hippocampus neurons in T2D rats. Moreover, taurine supplement also inhibited high glucose-induced apoptosis in HT-22 cell in vitro. Mechanistically, taurine increased the expression of NGF, phosphorylation of Trka, Akt, and Bad, as well as reduced cytochrome c release from mitochondria to cytosol. However, beneficial effects of taurine were blocked in the presence of anti-NGF antibody or Akt inhibitor. Taurine could inhibit hippocampus neuron apoptosis via NGF-Akt/Bad pathway. These results provide some clues that taurine might be efficient and feasible candidate for improvement of learning and memory ability in T2D rats.

Taurine protects against myelin damage of sciatic nerve in diabetic peripheral neuropathy rats by controlling apoptosis of schwann cells via NGF/Akt/GSK3ß pathway.

Diabetic peripheral neuropathy is a common complications of Type 2 Diabetes and its main pathological feature is myelin sheath damage of peripheral nerve that was induced by Schwann cells (SCs) apoptosis. Increasing evidence suggested that taurine might play a role in improving DPN because of its ability to prevent SCs apoptosis. In this study, we explore the effect of taurine on preventing SCs apoptosis and its underlying mechanism. Sprague Dawley rats were treated with streptozotocin to establish the diabetes model. Rats were randomly divided into control, diabetes, taurine treatment (as giving 0.5%, 1% and 2% taurine in drinking water) groups. RSC96 cell (a rat SCs line) was used for intervention experiments in vitro. Results showed that taurine significantly corrected morphology of damaged myelin sheath and inhibited SCs apoptosis in sciatic nerve of diabetic rats. Moreover, taurine prevented apoptosis of RSC96 cells exposed to high glucose. Mechanistically, taurine up-regulated NGF expression and phosphorylation levels of Akt and GSK3ß, while, blocking activation of NGF and phosphorylation of Akt and GSK3ß increased apoptosis of high glucose-exposed RSC96 cells with taurine supplement. These results revealed taurine improved the myelin sheath damage of sciatic nerve in diabetic rats by controlling SCs apoptosis via NGF/Akt/GSK3ß signaling pathways, which provides some clues that taurine might be effective and feasible candidate for the treatment of DPN.

Liver-directed gene therapy results in long-term correction of progressive familial intrahepatic cholestasis type 3 in mice.

BACKGROUND & AIMS: Progressive familial intrahepatic cholestasis type 3 (PFIC3), for which there are limited therapeutic options, often leads to end-stage liver disease before adulthood due to impaired ABCB4-dependent phospholipid transport to bile. Using adeno-associated virus serotype 8 (AAV8)-mediated gene therapy, we aimed to restore the phospholipid content in bile to levels that prevent liver damage, thereby enabling stable hepatic ABCB4 expression and long-term correction of the phenotype in a murine model of PFIC3. METHODS: Ten-week-old Abcb4-/- mice received a single dose of AAV8-hABCB4 (n = 10) or AAV8-GFP (n = 7) under control of a liver specific promoter via tail vein injection. Animals were sacrificed either 10 or 26 weeks after vector administration to assess transgene persistence, after being challenged with a 0.1% cholate diet for 2 weeks. Periodic evaluation of plasma cholestatic markers was performed and bile duct cannulation enabled analysis of biliary phospholipids. Liver fibrosis and the Ki67 proliferation index were assessed by immunohistochemistry. RESULTS: Stable transgene expression was achieved in all animals that received AAV8-hABCB4 up to 26 weeks after administration. AAV8-hABCB4 expression restored biliary phospholipid excretion, increasing the phospholipid and cholesterol content in bile to levels that ameliorate liver damage. This resulted in normalization of the plasma cholestatic markers, alkaline phosphatase and bilirubin. In addition, AAV8-hABCB4 prevented progressive liver fibrosis and reduced hepatocyte proliferation for the duration of the study. CONCLUSION: Liver-directed gene therapy provides stable hepatic ABCB4 expression and long-term correction of the phenotype in a murine model of PFIC3. Translational studies that verify the clinical feasibility of this approach are warranted. LAY SUMMARY: Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a severe genetic liver disease that results from impaired transport of lipids to bile, which makes the bile toxic to liver cells. Because therapeutic options are currently limited, this study aims to evaluate gene therapy to correct the underlying genetic defect in a mouse model of this disease. By introducing a functional copy of the missing gene in liver cells of mice, we were able to restore lipid transport to bile and strongly reduce damage to the liver. The proliferation of liver cells was also reduced, which contributes to long-term correction of the phenotype. Further studies are required to evaluate whether this approach can be applied to patients with PFIC3.

NGF protects bone marrow mesenchymal stem cells against 2,5-hexanedione-induced apoptosis in vitro via Akt/Bad signal pathway.

Mesenchymal stem cell transplantation has been proposed as a promising therapy for regeneration of damaged tissues-especially, bone marrow mesenchymal stem cell (BMSC) transplantation therapy is considered to be an effective strategy for treating various injures in recent years. However, poor viability of transplanted BMSCs in injured tissues has limited their therapeutic efficiency. Nerve growth factor (NGF) has been reported to be a pro-survival factor in series of cells. Moreover, NGF could improve BMSC viability and activate anti-apoptotic pathway. Therefore, we are interested to know whether NGF promoted BMSC survival in transplanted tissue. In this study, we investigated the protective effect and potential mechanisms of NGF against apoptosis of BMSCs in vitro. 2,5-hexanedione (HD) was the apoptosis inducer. BMSCs were treated with 40 mM HD and different concentrations of NGF (0, 50, 100, 200 µg/L) together for 24 h. Results showed that NGF treatment increased the viability of BMSCs exposed to HD. Moreover, NGF effectively suppressed HD-induced apoptosis which was characterized by inhibiting caspase-3 activity, as well as mitochondrial transmembrane potential depolarization. Mechanistically, it was found that NGF promoted phosphorylation of Akt and Bad, which is TrkA dependent. However, K252a and MK-2206 (TrkA and Akt inhibitor, respectively) suppressed the anti-apoptosis of NGF, indicating the protective effect of NGF on BMSCs apoptosis via a novel Akt/Bad pathway. The findings suggested that NGF may be used as an effective protective agent against BMSC apoptosis so as to promote the survival rate of transplanted BMSCs and their tissue repair capability.

A novel UGT1A1 gene mutation causing severe unconjugated hyperbilirubinemia: a case report.

BACKGROUND: Crigler-Najjar syndrome (CNs) presents as unconjugated hyperbilirubinemia, as a result of UGT1A1 deficiency, and can be categorized in a severe (type I) and mild (type II) phenotype. CNs type II patients usually benefit from phenobarbital treatment that induces residual UGT1A1 activity. CASE PRESENTATION: Here we present a CNs type II patient that is not responsive to phenobarbital treatment, which can be explained by two heterozygous mutations in the UGT1A1 gene. A 3 nucleotide insertion in the HNF-1α binding site in the proximal promoter previously reported in a Crigler-Najjar patient on one allele and a novel two nucleotide deletion in exon 1, resulting in a frameshift and a premature stop codon. CONCLUSION: In newly diagnosed CNs patients with unconjugated bilirubin levels consistent with CNs type II but that are unresponsive to phenobarbital treatment, disruption of the HNF-1α binding site in the proximal promoter should be considered as a probable cause. Upon confirming a mutation in the HNF-1α site, phenobarbital treatment should be stopped or at least be reconsidered because of its sedative effects and its teratogenic properties.

Correction to: Taurine Ameliorates High Glucose Induced Apoptosis in HT-22 Cells.

Affiliations of authors Muhammad Shahbaz and Shahid Alam were incorrect in the published book. This has now been corrected as below.

Anti-apoptotic Effect of Taurine on Schwann Cells Exposed to High Glucose In Vitro.

It was reported that apoptosis of Schwann cells could increase in the diabetic rats. The studies showed that taurine inhibited apoptosis in a variety of cells. However, there were few reports on studying the protection of taurine against apoptosis of Schwann cells induced by high glucose (HG) and the underlying mechanism. In our study, the cells were divided into five groups: Control: the normal medium; HG group: 50 mM high glucose; T1: 50 mM high glucose+Taurine (10 mM) group; T2: 50 mM high glucose+Taurine (20 mM) group; T3: 50 mM high glucose+Taurine (40 mM) group. We used MTT and Tunel assays to measure the cell viability and apoptosis, respectively. Then, we also used western blotting to detect the protein levels of apoptosis-related protein. The results demonstrate that taurine promoted cell viability and decreased apoptosis in RSC96 cells exposed to HG. Furthermore, taurine markedly improved imbalance of Bax and Bcl-2, inhibited the translocation of Cytochrome C (Cyt C) from mitochondria to cytosol and reduced caspase-3 activity in HG-induced RSC96 cells. Our results indicate that taurine protect against apoptosis of Schwann cells induced by HG via inhibiting mitochondria-dependent caspase-3 pathway.

Protection of Taurine Against Neurotoxicity Induced by Arsenic in Primary Cortical Neurons.

Our group previously reported that taurine has a protective capacity on the hippocampus and cerebellum of arsenic (As)-exposed mouse. In the present study, we explore whether taurine demonstrates protection against As toxicity in primary cortical neurons. Primary cortical neurons were exposed to various concentrations of arsenite and cell viability was assessed to confirm the toxicity of As on cortical neurons. The protection of taurine was examined after primary cortical neurons were treating with arsenite and taurine for 24 h. The cell viability was examined by MTT and caspase-3 activity assay. The expression of Bax and Bcl-2 was determined by western blot. The results showed that As exposure reduced cell viability and enhanced the activity of caspase-3, which were markedly inhibited by taurine treatment. The expression of Bax and Bcl-2 were disturbed by As exposure, which were reversed by taurine. These results indicated that taurine expose protective effect on As-exposed primary cortical neurons and its mechanism maybe involved the regulation of Bax/Bcl-2.

Protective Effect of Taurine on Apoptosis of Spinal Cord Cells in Diabetic Neuropathy Rats.

Diabetes mellitus (DM) is a condition characterized by chronic hyperglycemia, which leads to diabetic neuropathy and apoptosis in the spinal cord. Taurine has been found to ameliorate the diabetic neuropathy and control apoptosis in various tissues. However, there are few reports that discuss the direct relationship between spinal cord and anti-apoptotic effect of taurine. In this study, DM was induced in male SD rats with STZ @ 25 mg/Kg of body weight in combination with high fat diet. After 2 weeks, they were divided into four groups as DM: diabetic rats, T1 (0.5%), T2 (1%) and T3 (2%) taurine solution, while control group was non-diabetic rats (no treatment). The results showed that DM increased apoptosis, decreased phosphorylated Akt and Bad. DM decreased expression of Bcl-2 and increased the Bax. Moreover, the release of cytochrome c into cytosol was increased in DM and activation of caspase-3 was also increased. However, taurine reversed all these abnormal changes in a dose dependent manner. Our results suggested the involvement of Akt/Bad signaling pathway and mitochondrial apoptosis pathway in protective effect of taurine against apoptosis in the spinal cord of diabetic rats. Therefore, taurine may be a potential medicine against diabetic neuropathy by controlling apoptosis.

Taurine Ameliorates High Glucose Induced Apoptosis in HT-22 Cells.

Diabetes causes memory loss. Hippocampus is responsible for memory and increased apoptosis was found in diabetes patients. Taurine improved memory in diabetes condition. However, mechanism is unclear. In current study, hippocampal cell line HT-22 cells were subjected to analysis as five groups i.e. Control, High glucose (HG) at concentration of 150 mM, HG + 10 mM (T1), 20 mM (T2) and 40 mM (T3) taurine solution. TUNEL assay showed that HG increased the number of apoptotic cell significantly while taurine reduced apoptosis. Taurine increased phosphorylation of Akt in HT-22 cell treated with HG, and increased phosphorylation of Bad (p-Bad) was seen suggesting involvement of Akt/Bad signaling pathway. Expression of Bcl-2 was reduced in HG group but taurine improved this. Bax expression showed opposite trend. This indicated that taurine may reduce apoptosis by controlling balance of Bcl-2 and Bax. When the activation of Akt was blocked by using of perifosine, the effect of taurine disappears either partially or altogether. Thus, it was clear that taurine reduces apoptosis via Akt/Bad pathway in HT-22 cells exposed to HG which further improves downstream balance of Bcl-2 and Bax. This mechanism may be involved in apoptosis of hippocampus cells in diabetic condition.

Taurine Promotes Neuritic Growth of Dorsal Root Ganglion Cells Exposed to High Glucose in Vitro.

Diabetic neuropathy (DN) is the most common chronic complication of DM and its major pathological changes show axonal dysfunction, atrophy and loss. However, there are few reports that taurine promotes neurite growth of dorsal root ganglion (DRG) cells. In current study, DRG neurons were exposed to high glucose (HG) with or without taurine. The neurite outgrowth of DRG neurons was observed by fluorescent immunohistochemistry method. Expression of Gap-43, Akt, phosphorylated Akt, mTOR and phosphorylated mTOR was determined by Western blot assay. Our results showed that HG significantly decreased the neurite outgrowth and expression of Gap-43 in DRG neurons. Moreover, phosphorylated levels of Akt and mTOR were downregulated in DRG neurons exposed to HG. On the contrary, taurine supplementation significantly reversed the decreased neurite outgrowth and Gap-43 expression, and the downregulated phosphorylated levels of Akt and mTOR. However, the protective effects of taurine were blocked in the presence of PI3K antagonists LY294002 or Akt antagonists Perifosine. These results indicate that taurine promotes neurite outgrowth of DRG neurons exposed to HG via activating Akt/mTOR signal pathway.