Biomedical subjects

H Chen

Publications and source records attributed to H Chen.

At least 271 records · Page 15Linked to original sources

PubMed2001

TGF-beta(1) modulates NOS expression and phosphorylation of Akt/PKB in rat myocytes exposed to hypoxia-reoxygenation.

Myocardial hypoxia-reoxygenation (H-R) is associated with upregulation of inducible nitric oxide synthase (iNOS), decrease in endothelial NOS (eNOS), and increase in protein kinase B (PKB). Previous work also shows that transforming growth factor-beta(1) (TGF-beta(1)) can attenuate myocardial injury induced by H-R. We examined the modulation of NOS and PKB expression in response to H-R by TGF- beta(1). Myocytes from Sprague-Dawley rat hearts were cultured and exposed to hypoxia (95% N(2)-5% CO(2), PO(2) ~30 mmHg) for 24 h and reoxygenation (95% air-5% CO(2)) for 3 h. Myocytes were then examined for lactate dehydrogenase (LDH) release, iNOS activity (conversion of L-[(3)H]arginine to L-[(3)H]citrulline), iNOS and eNOS expression, and PKB phosphorylation. H-R alone resulted in myocyte injury, upregulation of iNOS activity and expression, decrease in eNOS expression, and increase in PKB phosphorylation (all P < 0.05 vs. cells cultured in normoxic conditions). Treatment of myocytes with TGF-beta(1) (1 ng/ml) resulted in a reduction in LDH release, attenuation of the alterations in NOS expression (both iNOS and eNOS), and PKB phosphorylation in response to H-R (all P < 0.05 vs. H-R alone). These observations suggest that TGF-beta(1) decreases H-R injury and attenuates alterations in NOS and PKB phosphorylation in myocytes exposed to H-R.

Animals↗

PubMed2001

Interleukin-6 signaling and embryonic mouse submandibular salivary gland morphogenesis.

Interleukin-6 (IL-6) is a multifunctional cytokine that mediates cell growth, differentiation, and survival. It was the objective of the present study to investigate the possible function(s) of IL-6 signaling in embryonic mouse submandibular salivary gland (SMG) morphogenesis. After characterizing in vivo mRNA and protein expression of various constituents of this pathway, we utilized in vitro strategies to investigate the phenotypic outcomes of enhanced IL-6-induced signaling and immunoperturbation of IL-6 binding to cognate receptors. These experiments demonstrate: (1) there is a significant increase of IL-6 mRNA with progressive SMG development, and that this is highly correlated with TNF transcript levels; (2) IL-6 and its cognate receptors are immunolocalized in SMG branching epithelia from the canalicular stage to the late terminal bud stage, as are other constituents of the IL-6 pathway; (3) as compared to controls, IL-6-supplemented explants exhibit a substantial increase in overall size and in the number of ductal branches and terminal buds, as well as a highly significant increase in epithelial cell proliferation; (4) SMG explants cultured in the presence of anti-IL-6 neutralizing antibodies exhibit a marked decrease in epithelial ducts and terminal buds, concomitant with a significant decline in cell proliferation and a highly significant increase in apoptosis. Taken together, our experimental results indicate that IL-6 signaling is important to SMG developmental homeostasis.

Animals↗

PubMed2001

Association between the Ser9Gly polymorphism of the dopamine D3 receptor gene and tardive dyskinesia in Chinese schizophrenic patients.

It has been suggested that dopamine D3 receptor (DRD3) may have important implications for antipsychotic-induced tardive dyskinesia (TD). Previous studies have demonstrated an association between a serine to glycine polymorphism in the first exon of the DRD3 gene and TD; however, the results have been inconsistent. Therefore, we have replicated these studies using a Chinese sample population. A total of 115 schizophrenic patients from chronic wards were assessed for TD severity using the Abnormal Involuntary Movements Scale (AIMS) and were subsequently genotyped for the DRD3 polymorphism. The mean AIMS score for patients carrying the heterozygote (DRD3(ser-gly)) was significantly greater than for those with the homozygotes (DRD3(ser-ser) and DRD3(gly-gly)). Our results are in line with a previous report, the results of which suggest that the presence of the DRD3(ser-gly) genotype may be a risk factor for the development of TD in patients treated with antipsychotics.

Adolescent↗

PubMed2001

Cartilage oligomeric matrix protein (thrombospondin-5) is expressed by human vascular smooth muscle cells.

Cartilage oligomeric matrix protein (COMP/thrombospondin [TSP]-5) belongs to the thrombospondin gene family and is an extracellular glycoprotein found predominantly in cartilage and tendon. To date, there is limited evidence of COMP/TSP-5 expression outside of the skeletal system. The aim of the present study was to investigate the expression of COMP/TSP-5 in cultured human vascular smooth muscle cells and human arteries. COMP/TSP-5 mRNA and protein expression was detected in cultured human vascular smooth muscle cells with both Northern blotting and immunoprecipitation. Serum, as well as transforming growth factor (TGF)beta1 and TGF-beta3, stimulated COMP/TSP-5 mRNA expression. COMP/TSP-5 was detected in normal as well as atherosclerotic and restenotic human arteries with immunohistochemistry. The majority of COMP/TSP-5 was expressed in close proximity to vascular smooth muscle cells. In vitro attachment assays demonstrated strong adhesion of smooth muscle cells to COMP/TSP-5-coated surfaces, with the majority of cells spreading and forming stress fibers. In addition, COMP/TSP-5 supported the migration of smooth muscle cells in vitro. The present study shows that COMP/TSP-5 is present in human arteries and may play a role in the adhesion and migration of vascular smooth muscle cells during vasculogenesis and in vascular disease settings such as atherosclerosis.

Cartilage↗

PubMed2001

Reduction and restoration of mitochondrial dna content after focal cerebral ischemia/reperfusion.

BACKGROUND AND PURPOSE: Oxidative damage of mitochondrial DNA (mtDNA) in the ischemic brain is expected after ischemia/reperfusion injury. A recent study demonstrated limited patterns of mtDNA deletion in the brain after ischemia/reperfusion. We studied the ischemia/reperfusion-induced global changes of mtDNA integrity and its restoration in a rat model of transient focal ischemia in vivo. METHODS: Changes in mtDNA content in the ischemic brain were assessed with the use of a rat stroke model featuring transient severe ischemia confined to the cerebral cortex of the right middle cerebral artery territory for 30 or 90 minutes. A new long polymerase chain reaction method, using mouse DNA as an internal standard, was applied to measure the relative content of intact rat mtDNA. Southern hybridization following alkaline gel electrophoresis was conducted in a parallel study to confirm long polymerase chain reaction results. RESULTS: A reduction in mtDNA content was found after ischemia for 30 and 90 minutes. The mtDNA was restored to near nonischemic levels 24 hours after 30- but not 90-minute ischemia. CONCLUSIONS: These results confirm that ischemia/reperfusion causes mtDNA damages. Restoration of the mtDNA content to nonischemic levels after 30-minute ischemia raises the possibility that mtDNA repair or repletion occurs after brief ischemia.

Animals↗

PubMed2001

Angiotensin II via activation of type 1 receptor upregulates expression of endoglin in human coronary artery endothelial cells.

Transforming growth factor-beta1 and its subtype receptor endoglin are key components in angiogenesis. We explored the role of angiotensin (Ang) II in the expression of endoglin and the underlying intracellular signaling mechanism in human coronary artery endothelial cells. Incubation of cells with Ang II upregulated endoglin expression in a concentration- and time-dependent manner (maximal effect with 10(-6) mol/L Ang II at 24 hours). The Ang II type 1 receptor blocker losartan, but not the type 2 receptor blocker PD 123,319, completely blocked the effect of Ang II. In parallel experiments, the mitogen-activated protein kinase inhibitor PD 098,059 fully inhibited the effect of Ang II on the expression of endoglin. Incubation of endothelial cells with Ang II also increased the expression of transforming growth factor-beta1 and -beta2 receptors and simultaneously decreased the levels of transforming growth factor-beta1. These effects of Ang II were also attenuated by losartan. We propose that Ang II via its type 1 receptor activation modulates the expression of transforming growth factor-beta1 receptors in human coronary endothelial cells. The activation of mitogen-activated protein kinase plays an important role in this process. These observations provide a new clue regarding the regulatory effect of Ang II on vascular remodeling after injury.

Angiotensin II↗

PubMed2001

Aspergillus fumigatus-induced allergic airway inflammation alters surfactant homeostasis and lung function in BALB/c mice.

The differential regulation of pulmonary surfactant proteins (SPs) is demonstrated in a murine model of Aspergillus fumigatus (Af )-induced allergic airway inflammation and hyperresponsiveness. BALB/c mice were sensitized intraperitoneally and challenged intranasally with Af extract. Enzyme-linked immunosorbent assay analysis of serum immunoglobulin (Ig) levels in these mice showed markedly increased total IgE and Af-specific IgE and IgG1. This was associated with peribronchial/perivascular tissue inflammation, airway eosinophilia, and secretion of interleukin (IL)-4 and IL-5 into the bronchoalveolar lavage fluid (BALF). Functional analysis revealed that in comparison with nonsensitized mice, allergic sensitization and challenge resulted in significant increases in acetylcholine responsiveness. To analyze levels of SPs, the cell-free supernate of the BALF was further fractionated by high-speed (20,000 x g) centrifugation. After sensitization and challenges, the pellet (large-aggregate fraction) showed a selective downregulation of hydrophobic SPs SP-B and SP-C by 50%. This reduction was reflected by commensurate decreases in SP-B and SP-C messenger RNA (mRNA) expression of the lung tissue of these animals. In contrast, there was a 9-fold increase in SP-D protein levels in the 20,000 x g supernate without changes in SP-D mRNA. The increased levels of SP-D showed a significant positive correlation with serum IgE (r = 0.85, P < 0.001). Tissue mRNA and protein levels of SP-A in either the large- or the small-aggregate fractions were unaffected. Our data indicate that allergic airway inflammation induces selective inhibition of hydrophobic SP synthesis accompanied by marked increases in the lung collectin SP-D protein content of BALF. These changes may contribute significantly to the pathophysiology of Af-induced allergic airway hyperresponsiveness.

Animals↗

PubMed2001

Modulation of T-cell responses to alloantigens by TR6/DcR3.

TR6 (DcR3) is a new member of the TNF receptor (TNFR) family that lacks a transmembrane domain in its sequence, indicating that it is a secreted molecule. TR6 can bind to FasL and prevent FasL-induced apoptosis; it can also associate with LIGHT, another TNF family member. The role of TR6 in immune responses was investigated in this study. According to flow cytometry, recombinant human TR6-Fc binds to human LIGHT expressed on 293 cells or on activated human T cells and competes with the LIGHT receptor TR2 for the binding to LIGHT on these cells. Human TR6 could cross-react with mouse LIGHT in immunoprecipitation. TR6-Fc also downregulates cytotoxic T lymphocyte activity in vitro and graft-versus-host responses in mice. Moreover, TR6-Fc modulates lymphokine production by alloantigen-stimulated mouse T cells. TR6-Fc ameliorated rejection response to mouse heart allograft. These results indicate that TR6 can dampen T-cell responses to alloantigens. Such regulatory effects of TR6 probably occur via interference with interaction between pairs of related TNF and TNFR family members, LIGHT/TR2 being one of the possible candidate pairs.

Animals↗

PubMed2001

Development of a fluorescence based high throughput assay for antagonists of the human chorionic gonadotropin receptor extracellular domain: analysis of peptide inhibitors.

A simple method for prompt fluorescent detection of inhibitors of human chorionic gonadotropin (hCG) binding to the extracellular domain of the human luteinizing hormone/chorionic gonadotropin (hLH/CG) receptor was developed for high throughput screening (HTS). Construction and analysis of a recombinant phage that displays the extracellular binding domain of the hLH/CG receptor on its surface and specifically binds hCG was previously described. To facilitate the identification of molecules that disrupt the interaction of hCG with its receptor, a method for prompt fluorescent detection of these phage bound to hCG was developed. This technique is extremely sensitive and employs fluorescent labels (PBXL dyes) that are derived from red and blue-green algae. Antibodies labeled with PBXL dye were able to specifically detect phage that display the extracellular domain of the hLH/CG receptor when bound to hCG immobilized in 96-well microplates. Decreases in fluorescence correlate with the concentration of exogenous hCG or hCG antagonists in the assay. This prompt fluorescence detection assay was optimized in a 96-well format as a model system for HTS applications that target the receptors for the group of hormones known as the gonadotropins. Low-affinity molecules that disrupt binding of the phage-displayed receptor extracellular domain to hCG can be rapidly identified in this high throughput screen.

Automation↗

PubMed2001

Gene expression in Brown Norway rat Leydig cells: effects of age and of age-related germ cell loss.

There is a marked reduction in circulating T and a commensurate decrease in Leydig cell function in males during aging. Aging is also accompanied by progressive loss of germ cells, leading to testicular atrophy. However, in aged animals, there is no difference in T production by Leydig cells from nonregressed testes and from regressed testes. We hypothesize that there are changes in Leydig cell gene expression that accompany aging, and that different changes in gene expression result from testicular regression. To test this hypothesis, the expression of stress response genes was compared in Leydig cells isolated from young rat testes, from aged testes that were not regressed, and from aged testes that were regressed, using an array approach. Similar numbers of transcripts (n = 56-63) were detected in Leydig cells isolated from all three groups of rats. Among these, 21 transcripts were increased in Leydig cells of testes from aged nonregressed animals compared with cells from young animals; 23 were increased with subsequent testicular regression. Only 3 of these transcripts were in common. Thus, age and testicular regression affected Leydig cell transcripts in dramatically different ways. Furthermore, none of the transcripts that decreased when comparing Leydig cells of young and aged nonregressed animals were the same as those that decreased when comparing aged nonregressed and aged regressed animals. In individual gene families, the steady state concentrations of transcripts in Leydig cells from aging and aging regressed testes often differed. Thus, there are major differences in the expression of a wide variety of stress response genes in Leydig cells associated with aging and testicular regression.

Aging↗

PubMed2001

Parathyroid hormone stimulates fra-2 expression in osteoblastic cells in vitro and in vivo.

PTH and PTH-related protein (PTHrP) are key mediators of skeletal development and homeostasis through their activation of the PTH-1 receptor. Previous studies have found that several AP-1 family members are regulated by PTH, such as c-fos, fra-1, and c-jun. There are numerous genes in the bone microenvironment that contain AP-1 sites, and different Fos family members are reported to have opposing transcriptional activities at AP-1 sites. The purpose of this study was to identify the effects of PTH on expression of the AP-1 protein complex member, fra-2, to extend our understanding of transcriptional regulators of PTH action. PTH induction of fra-2 messenger RNA (mRNA) levels in MC3T3-E1 preosteoblastic cells was maximal with 0.1 microM PTH (1-34). The expression in vitro was greatest 1 h after treatment and was present with N-terminal PTH but not PTH (7-34) or (53-84). Cycloheximide treatment induced fra-2 expression, and actinomycin D inhibited basal and PTHrP-induced expression. AP-1 protein in nuclear extracts of MC3T3-E1 cells was increased with PTH treatment at 3 h and consisted of high levels of Fra-2 protein, as evidenced by a supershift in an electrophoretic mobility shift assay and Western blot analysis. Up-regulation of steady-state fra-2 mRNA was also noted in vivo, where injection of PTH (1-34) (20 microgram) resulted in a more-than-7-fold maximal increase in fra-2 mRNA expression in the calvaria of mice, after 1 h of treatment. These data add to the transcriptional mediators induced by PTH and suggest that the interplay of AP-1 family members will provide insight into regulatory pathways of PTH and PTHrP for their anabolic and catabolic actions in bone.

Animals↗

PubMed2001

Phenotypes Associated with SHOX Deficiency.

Leri-Weill dyschondrosteosis (LWD) (MIM 127300) is a dominantly inherited skeletal dysplasia characterized phenotypically by Madelung wrist deformity, mesomelia, and short stature. LWD can now be defined genetically by haploinsufficiency of the SHOX (short stature homeobox-containing) gene. We have studied 21 LWD families (43 affected LWD subjects, including 32 females and 11 males, ages 3-56 yr) with confirmed SHOX abnormalities. We investigated the relationship between SHOX mutations, height deficit, and Madelung deformity to determine the contribution of SHOX haploinsufficiency to the LWD and Turner syndrome (TS) phenotypes. Also, we examined the effects of age, gender, and female puberty (estrogen) on the LWD phenotype. SHOX deletions were present in affected individuals from 17 families (81%), and point mutations were detected in 4 families (19%). In the LWD subjects, height deficits ranged from -4.6 to +0.6 SD (mean +/- SD = -2.2 +/- 1.0). There were no statistically significant effects of age, gender, pubertal status, or parental origin of SHOX mutations on height z-score. The height deficit in LWD is approximately two thirds that of TS. Madelung deformity was present in 74% of LWD children and adults and was more frequent and severe in females than males. The prevalence of the Madelung deformity was higher in the LWD vs. a TS population. The prevalence of increased carrying angle, high arched palate, and scoliosis was similar in the two populations. In conclusion, SHOX deletions or mutations accounted for all of our LWD cases. SHOX haploinsufficiency accounts for most, but not all, of the TS height deficit. The LWD phenotype shows some gender- and age-related differences.

Adolescent↗

PubMed2001

Evidence that longer androgen receptor polyglutamine repeats are a causal factor for genital abnormalities.

Moderate to severe undermasculinized genitalia was recently shown to be associated with longer polyglutamine repeats within the androgen receptor [AR(Gln)n]. However, it was unknown whether this was because longer AR(Gln)n contributed to the: 1) etiology; 2) severity; and/or 3) testicular maldescent. Therefore, AR(Gln)n length in 175 males with abnormal genitalia were analyzed according to etiology (known or unknown), severity (complete, severe, and moderate), or testis position (abdominal, inguinal, or scrotal). Etiology (P = 0.01) and severity (P = 0.02) but not testis position (P = 0.52) were associated with AR(Gln)n length. The association between the severity of the genital abnormalities and AR(Gln)n length was due to the close association of severity with the etiology (P < 0.0001). A highly selected group with moderate to severe genital abnormalities and multiple criteria to exclude known etiological factors had a greater AR(Gln)n length (mean, 25.33) than all other samples (mean, 23.11; P = 0.0004). The results suggest that AR(Gln)n length does not influence the severity of undermasculinization or testis descent but instead contributes to the causation of genital abnormalities in a subset of patients. These findings, together with a demonstrated relationship between severity and multifactorial etiology, are incorporated into a proposed model for the involvement of AR(Gln)n length in genital abnormalities.

Cryptorchidism↗

PubMed2001

Phosphorylation of PTP1B at Ser(50) by Akt impairs its ability to dephosphorylate the insulin receptor.

PTP1B is a protein tyrosine phosphatase that negatively regulates insulin sensitivity by dephosphorylating the insulin receptor. Akt is a ser/thr kinase effector of insulin signaling that phosphorylates substrates at the consensus motif RXRXXS/T. Interestingly, PTP1B contains this motif (RYRDVS(50)), and wild-type PTP1B (but not mutants with substitutions for Ser(50)) was significantly phosphorylated by Akt in vitro. To determine whether PTP1B is a substrate for Akt in intact cells, NIH-3T3(IR) cells transfected with either wild-type PTP1B or PTP1B-S50A were labeled with [(32)P]-orthophosphate. Insulin stimulation caused a significant increase in phosphorylation of wild-type PTP1B that could be blocked by pretreatment of cells with wortmannin or cotransfection of a dominant inhibitory Akt mutant. Similar results were observed with endogenous PTP1B in untransfected HepG2 cells. Cotransfection of constitutively active Akt caused robust phosphorylation of wild-type PTP1B both in the absence and presence of insulin. By contrast, PTP1B-S50A did not undergo phosphorylation in response to insulin. We tested the functional significance of phosphorylation at Ser(50) by evaluating insulin receptor autophosphorylation in transfected Cos-7 cells. Insulin treatment caused robust receptor autophosphorylation that could be substantially reduced by coexpression of wild-type PTP1B. Similar results were obtained with coexpression of PTP1B-S50A. However, under the same conditions, PTP1B-S50D had an impaired ability to dephosphorylate the insulin receptor. Moreover, cotransfection of constitutively active Akt significantly inhibited the ability of wild-type PTP1B, but not PTP1B-S50A, to dephosphorylate the insulin receptor. We conclude that PTP1B is a novel substrate for Akt and that phosphorylation of PTP1B by Akt at Ser(50) may negatively modulate its phosphatase activity creating a positive feedback mechanism for insulin signaling.

3T3 Cells↗

PubMed2001

Effects of ethanol on the ultrastructure of the hamster femur.

Several previous studies have indicated that chronic ingestion of ethanol exerts harmful effects on bones. However, few data are available concerning the effects of ethanol on the ultrastructure of bone. To further elucidate the effects of ethanol on bone, we studied the morphology of femur in golden hamsters after long-term treatment with ethanol. Six-week-old male hamsters were divided into 4 groups. Ethanol-treated animals were given ethanol at a concentration of 7% with food and water freely available, whereas the pair-fed animals (weight-matched to ethanol hamsters) had tap water available as the only drinking fluid. The femur weight, blood ethanol and serum calcium concentrations were determined after 3 and 5 months. The bone mineral density (BMD) of the whole body was measured before and after the experiment. Femurs of both sides were dissected and processed for morphometric measurement, light microscopy, scanning and transmission electron microscopy. In the ethanol-treated hamsters, BMD of the whole body and the weight of femur tended to decrease when compared with those of the controls. Light microscopy and scanning electron microscopy showed that the trabecula in the distal end of the femur from ethanol-treated hamsters were thinner than those of the controls. We also observed the disrupted swollen mitochondria of the femoral osteoblasts and osteocytes in the ethanol-treated hamsters. No significant difference in serum calcium levels and femoral osteoclasts was found. These results indicate that long-term treatment with ethanol results in disruption of femoral osteoblasts and reduction of bone mass in trabecular bone.

Alcoholism↗

PubMed2001

Morphological identification of the lipid-storing cells in golden hamster parathyroid glands after vitamin A treatment.

We investigated hamster parathyroid glands of different ages using electron microscopy and found a new cell type in young, adult and senile hamsters. Theses special cells were located in interstitial tissues and invariably contained several lipid droplets within the cytoplasm. The cells showed an elongated spindle with some cell processes. The cells contained small Golgi complexes and moderate cisternae of the granular endoplasmic reticulum. The morphological characteristics of these cells were mostly the same as those of lipid-storing cells in other organs (Yamada and Hirosawa, 1976). After vitamin A administration, the lipid droplets in these cells markedly increased in number and also in volume density. The other morphological features of these cells resembled those of the control animals. We called these cells parathyroid lipid-storing cells. They may incorporate and store vitamin A within the lipid droplets. They can be classified as one of the cellular components in hamster parathyroid gland.

Age Factors↗

PubMed2001

Determination of menadione sodium bisulfite in pharmaceutical preparations by flow-injection on-line photochemical spectrofluorometry.

A flow-injection on-line photochemical spectrofluorometry (FI-PF) was developed for the determination of menadione sodium bisulfite (MSB) using acetone and sodium sulfite as sensitizing reagents. An injected sample band carried by a water stream was on-line merged with a mixed NaOH, Na2SO3 and acetone solution in a "T" connector. It was then driven to pass a knotted PTFE photochemical reactor (0.5 mm i.d. x 200 cm, KR) that was freely coiled around a 6-W low-pressure mercury lamp. While passing the KR, MSB was derived into an intensively fluorescent compound that was on-line delivered into a flow-through cell and detected therein at an emission wavelength of 459 nm and an excitation wavelength of 336 nm. Under optimized conditions a detection limit of 0.38 microg l(-1) was achieved at a sampling rate of 90 h(-1). Eleven determinations of 0.5 mg l(-1) and 0.05 mg l(-1) MSB standard solution gave RSDs of 0.75% and 1.3%, respectively. The calibration curve was linear in the MSB concentration range 0.005-1.5 mg l(-1). The proposed method was successfully applied to assay the MSB content in MSB injection.

Flow Injection Analysis↗

PubMed2001

Overexpression of metallothionein in pancreatic beta-cells reduces streptozotocin-induced DNA damage and diabetes.

The release of reactive oxygen species (ROS) has been proposed as a cause of streptozotocin (STZ)-induced beta-cell damage. This initiates a destructive cascade, consisting of DNA damage, excess activation of the DNA repair enzyme poly(ADP-ribose) polymerase, and depletion of cellular NAD+. Metallothionein (MT) is an inducible antioxidant protein that has been shown to protect DNA from chemical damage in several cell types. Therefore, we examined whether overexpression of MT could protect beta-cell DNA and thereby prevent STZ-induced diabetes. Two lines of transgenic mice were produced with up to a 30-fold elevation in beta-cell MT. Cultured islets from control mice and MT transgenic mice were exposed to STZ. MT was found to decrease STZ-induced islet disruption, DNA breakage, and depletion of NAD+. To assess in vivo protection, transgenic and control mice were injected with STZ. Transgenic mice had significantly reduced hyperglycemia. Ultrastructural examination of islets from STZ-treated mice showed that MT prevented degranulation and cell death. These results demonstrate that MT can reduce diabetes and confirm the DNA damage mechanism of STZ-induced beta-cell death.

Animals↗