Biomedical subjects

Y Suresh

Publications and source records attributed to Y Suresh.

8 recordsLinked to original sources

PubMed2003

TGF beta1 induces multiple independent signals to regulate human trophoblastic differentiation: mechanistic insights.

Transforming growth factor-beta 1 (TGF beta1) plays a crucial role in controlling trophoblast growth and invasion. Loss of this key regulatory function provides the pathophysiological basis for several tumors, which are characterized by uncontrolled telomerase activity. We have shown earlier that telomerase activity is negatively regulated during terminal differentiation of human trophoblasts, and that TGF beta1 may be an important factor governing the transcription of human telomerase reverse transcriptase (hTERT) (the catalytic subunit of the telomerase complex) during this process. In the present study, we extend these observations to identify possible functional effectors of TGF beta1-induced loss in telomerase activity during human trophoblastic differentiation. We show that this regulation may involve the suppression of c-Myc and an increased production of Mad1. We also observed a simultaneous increase in the expression of cyclin-dependent-kinase inhibitors, p21, p27, p15 and p16, associated with a loss in expression of Cyclin-A2 and Cyclin-E. Thus, TGF beta1 may induce multiple independent signals to check the proliferative potential of human trophoblastic cells and allow their functional differentiation.

Cell Cycle Proteins↗

PubMed2003

Long-chain polyunsaturated fatty acids and chemically induced diabetes mellitus. Effect of omega-3 fatty acids.

In a previous study, we showed that prior oral feeding of oils rich in omega-3 eicosapentaenoic acid and docosahexaenoic acid and omega-6 gamma-linolenic acid and arachidonic acid prevent the development of alloxan-induced diabetes mellitus in experimental animals. We also observed that 99% pure omega-6 fatty acids gamma-linolenic acid and arachidonic acid protect against chemically induced diabetes mellitus. Here we report the results of our studies with omega-3 fatty acids. Alloxan-induced in vitro cytotoxicity and apoptosis in an insulin-secreting rat insulinoma cell line, RIN, was prevented by prior exposure of these cells to alpha-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid. Prior oral supplementation with alpha-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid prevented alloxan-induced diabetes mellitus. alpha-Linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid not only attenuated chemical-induced diabetes mellitus but also restored the anti-oxidant status to normal range in various tissues. These results suggested that omega-3 fatty acids can abrogate chemically induced diabetes in experimental animals and attenuate the oxidant stress that occurs in diabetes mellitus.

Administration, Oral↗

PubMed2003

Long-chain polyunsaturated fatty acids and chemically induced diabetes mellitus: effect of omega-6 fatty acids.

OBJECTIVE: We previously showed that prior oral supplementation of oils rich in omega-3, eicosapentaenoic acid and docosahexaenoic acid, and omega-6, gamma-linolenic acid and arachidonic acid, can prevent the development of alloxan-induced diabetes mellitus in experimental animals. But the effect of individual fatty acids on chemically induced diabetes mellitus is not known. We report the results of our studies with omega-6 fatty acids. METHODS: Alloxan-induced in vitro cytotoxicity and apoptosis in an insulin-secreting rat insulinoma cell line, RIN, was prevented by prior exposure of these cells to linoleic acid, gamma-linolenic acid, and arachidonic acid (AA) but not to dihomo-gamma-linolenic acid. Cyclo-oxygenase and lipoxygenase inhibitors did not block this protective action of AA. Prior oral supplementation with gamma-linolenic acid and pre- and simultaneous treatments with AA prevented alloxan-induced diabetes mellitus. RESULTS: Even though pretreatment with linoleic acid and dihomo-gamma-linolenic acid and simultaneous treatment with linoleic acid, gamma-linolenic acid, and dihomo-gamma-linolenic acid did not prevent the development of diabetes mellitus, the severity of diabetes was much less. The saturated fatty acid stearic acid and the monounsaturated fatty acid oleic acid were ineffective in preventing alloxan-induced diabetes mellitus. gamma-Linolenic acid and AA not only attenuated chemically induced diabetes mellitus but also restored the antioxidant status to normal range in various tissues. Changes in the concentrations of various fatty acids of the phospholipid fraction of plasma that occurred as a result of alloxan-induced diabetes mellitus also reverted to normal in the AA-treated animals. CONCLUSIONS: These results suggest that polyunsaturated fatty acids can prevent chemically induced diabetes in experimental animals and attenuate the oxidant stress that occurs in diabetes mellitus.

Alloxan↗

PubMed2001

Regulation of telomerase during human placental differentiation: a role for TGFbeta1.

The transient tumor-like attributes of the first-trimester placenta anchor the developing embryo to the uterine wall thus establishing a vital link between the mother and the fetus. Dysregulation of this invasive behavior and/or controlled proliferation of the placenta is associated with abnormal pregnancies. Several of these diseased states also exhibit aberrant telomerase activity, among other pathophysiological manifestations. Considering the strong correlation between telomerase activity and tumorigenesis, it was of interest to see whether the crucial processes of trophoblast proliferation and differentiation were brought about through the modulation of telomerase. Using two in vitro model systems of trophoblast differentiation, we demonstrate here that telomerase activity is negatively regulated during placental differentiation. We further show that this modulation is at the level of transcription of hTERT. We also propose a role for TGF beta1 in regulating telomerase activity in differentiating trophoblasts by down-regulating the expression of hTERT at the transcriptional level.

Blotting, Northern↗

PubMed2001

Protective action of arachidonic acid against alloxan-induced cytotoxicity and diabetes mellitus.

Previous studies showed that essential fatty acid (EFA) deficiency, conjugated linoleic acid and troglitazone exert a protective effect in animal models of diabetes mellitus. Here we show that alloxan-induced in vitro cytotoxicity and apoptosis in an insulin secreting rat insulinoma, RIN, cells can be prevented by arachidonic acid (AA) and that both cyclo-oxygenase and lipoxygenase inhibitors do not block this protective action. Alloxan-induced diabetes in male Wistar rats was also prevented by oral supplementation of AA, gamma-linolenic acid (GLA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). This protective action is best when the animals were pre-treated with the fatty acid. These results suggest that polyunsaturated fatty acids can prevent alloxan-induced diabetes mellitus in experimental animals and may be useful to prevent diabetes mellitus in the high-risk population.

Alloxan↗

PubMed2001

Oxidant stress, anti-oxidants and essential fatty acids in South Indian vegetarians and non-vegetarians.

Vegetarians are known to have a low incidence of cardiovascular diseases and lower blood pressure compared to non-vegetarians. The exact cause for this is not known. In the present study, it was found that, in general, vegetarians (female > males) have a higher concentrations of anti-oxidant enzymes: catalase and superoxide dismutase in their RBC membranes and lower levels of plasma lipid peroxides compared to non-vegetarians. Both male and female non-vegetarians were found to have a higher n-3/n-6 ratio compared to vegetarians. These results suggest that vegetarians have a higher anti-oxidant status and low levels of n-3 fatty acids. It remains to be seen whether this alterations in the oxidant and anti-oxidant status and n-3 concentrations explains the lower incidence of cardiovascular diseases and lower blood pressure in vegetarians.

Adult↗

PubMed2000

Preservation of the antioxidant status in chemically-induced diabetes mellitus by melatonin.

Oxidant stress is believed to be enhanced in patients with diabetes mellitus, which may lead to endothelial dysfunction and the development of atherosclerosis. In diabetes, hyperglycemia drives non-enzymatic glycation and oxidation of proteins and lipids which enhances the formation of advanced glycation end products (AGEs), which may be involved in the pathogenesis of diabetic vascular disease. The macrovascular complications of diabetes seem to be due to enhanced cellular oxidant stress by the interaction of AGEs with their receptor. It would be worthwhile to devise methods to reduce this oxidant stress. In alloxan-induced diabetic rats lipid peroxidation products were increased, while levels of nitric oxide glutathione peroxidase and superoxide dismutase were reduced. Melatonin restored these biochemical abnormalities to normalcy independent of hyperglycemia. This model can be used to study the role of oxidant stress in the development of macrovascular complications in diabetes mellitus.

Administration, Oral↗

PubMed1998

Leptin--the fat controller.

Obesity is a common health disorder in humans and is inherited genetically. Though several theories have been proposed in the past to understand the mechanisms underlying the control of obesity, the recent discovery of leptin (OB) has made the obesity research interesting. OB, a product of ob gene is a 16 KD protein, secreted by the adipocytes. It acts through its receptor (OB-R), which is a product of db gene. ob and OB-R in conjunction with neuropeptide Y, melanocyte stimulating hormone and melanocortin-4 receptor have been found to control adiposity. Though several issues pertaining to ob need to be addressed, it is anticipated that future treatment of obesity may depend on our understanding of the action(s) of leptin and its associated molecules and receptors.

Animals↗