Research
Publications

Dr. Schaffer's laboratory has been studying the effects of diabetes on heart function. Many of the molecular consequences of diabetes, such as altered osmotic balance, reduced protein synthesis, impaired energy metabolism and abnormal ion transport, are duplicated by incubation of isolated myocytes with high concentrations of glucose. Although glycosylation may play a role in the development of these abnormalities, osmotic imbalance also appears to be a contributing factor. The aim of more recent studies has been to clarify the basis of another property of the diabetic heart, the resistance to ischemic or hypoxic injury. This property is also duplicated by either chronically exposing myocytes to hyperosmotic medium or depleting the cell of an important organic osmolyte, taurine. Of particular interest are the effects of high glucose and osmotic stress on hypoxic-induced apoptosis. The information obtained will provide important insights into the regulation of programmed cell death in the heart.

Isolated Rat Myocytes in Primary Culture

1. Liu Y, Thornton JD, Cohen MV, Downey JM, and Schaffer SW. Streptozotocin-induced non-insulin-dependent diabetes protects the heart from infarction. Circulation 88:1273-1278 (1993).

2. Schaffer SW and Mozaffari M. Abnormal mechanical function in diabetes: relation to myocardial calcium handing. Coronary Artery Disease 7:109-115 (1996).

3. Ballard C. and Schaffer SW. Stimulation of the Na+-Ca2+ exchanger by phenylephrine, angiotensin II and endothelin 1. J. Mol. Cell. Cardiol. 28:11-17 (1996).

4. S.W. Schaffer, K. Nguyen, C. Ballard, N. Gardner, and J. Azuma.Regulation of Ca2+ Transport by Insulin and Taurine:Interaction at the Level of the Na+-Ca2+ Exchanger.In:R. Huxtable, J. Azuma, K. Kuriyama, N. Nakagawa and A. Baba (Eds.) Taurine 2:Basic and Clinical Aspects. Plenum Press, New York, pp. 551-560, 1996.

5. K. Takahashi, H. Hashimoto, A. Baba, S.W. Schaffer, and J. Azuma.Effects of Taurine on Angiotensin II-induced Expression of Immediate Early Response Genes in Cultured Neonatal Rat Heart Cells, In:R. Huxtable, J. Azuma, K. Kuriyama, N. Nakagawa and A. Baba (Eds.) Taurine 2:Basic and Clinical Aspects.Plenum Press, New York, pp. 297-304 (1996).

6. Allo SN, Bagby L and Schaffer SW. Taurine depletion, a novel mechanism for cardioprotection from regional ischemia. Am J. Physiol. 273:H1956-H1961 (1997).

7. Schaffer SW, Ballard-Croft, Boerth S and Allo SN. Mechanisms underlying depressed Na+-Ca2+ exchanger activity in the diabetic heart. Cardiovascular Research 34:129-136 (1997).

8. Mozaffari MS, Azuma J, Patel C and Schaffer SW. Renal excretory responses to saline load in taurine depleted and taurine supplemented rat. Biochem. Pharmacol. 54:619-624 (1997).

9. C. Ballard-Croft, M.S. Mozaffari, J. Azuma, and S. Schaffer.Interaction between Taurine and Angiotensin II:Modulation of Calcium Transport and Myocardial Contractile Function.Amino Acids 13:105-114 (1997).

10. M.S. Mozaffari, B.K. Warren, C.M. Russell, and S.W. Schaffer.Renal Function in the Noninsulin-dependent Diabetic Rat:Effect of Unilateral Nephrectomy.J. Pharmacol. Toxicol. Methods 37:197-203(1997).

11. M.S. Mozaffari, J. Azuma, C. Patel, and S.W. Schaffer.Renal Excretory Responses to Saline Load in the Taurine-Depleted and the Taurine-Supplemental Rat.Biochem. Pharmacol. 54:619-624(1997).

12. S.W. Schaffer, C. Ballard-Croft, K. Takahashi, and J. Azuma.Effect of Taurine Depletion on Angiotensin II-Mediated Modulation of Myocardial Function.IN:S. Schaffer, J.B. Lombardini and R.J. Huxtable (Eds.) Taurine 3:Cellular and Regulatory Mechanisms.Plenum Press, New York/London, Pp. 145-152 (1997).

13. S.W. Schaffer.Effect of Obesity on Myocardial Metabolism, Morphology and Function in the Obese (fa/fa) Zucker Rat.IN:M.A. Alpert and J.K. Alexander (Eds.) The Heart and Lung in Obesity.Futura Publshing, Armonk, New York, Pp. 11-24 (1998).

14. S.W. Schaffer, C. Ballard, and M.S. Mozaffari.Is There a Link Between Impaired Glucose Metabolism and Protein Kinase C Activity in the Diabetic Heart?Mol. Cell Biochem. 176:219-225 (1997).

15. K. Takahashi, S.W. Schaffer, and J. Azuma.Taurine-mediated Prevention of Intracellular Calcium Overload in Cultured Myocardial Cells During the Calcium Paradox.Amino Acids 13:1-11 (1997).

16. K. Takahashi, M. Azuma, A. Baba, S. Schaffer, and J. Azuma.Taurine Improves Angiotensin II-induced Hypertrophy of Cultured Neonatal Rat Heart Cells.IN:S. Schaffer, J.B. Lombardini and R.J. Huxtable (Eds.) Taurine 3:Cellular and Regulatory Mechanisms.Plenum Press, New York/London, Pp. 145-152 (1997)

17. K.Takahashi, M. Azuma, K. Taira, A. Baba, I. Yamamoto, S.W. Schaffer, and J. Azuma.Effect of Taurine on Angiotensin II-induced Hypertropy of Neonatal Rat Cardiac Cells.J. Cardiovasc. Pharmacol. 30:725-730 (1997).

18. M.S. Mozaffari, B.K. Warren, J. Azuma and S.W. Schaffer.Renal Excretory Responses to Taurine-Depleted Rats to Hypotonic and Hypertonic Saline Infusion.Amino Acids 15:109-116 (1998).

19. S.W. Schaffer, C. Ballard-Croft, J. Azuma, K. Takahashi, D.G. Kakhniashvili and T.E. Jenkins.Shape and Size Changes Induced by Taurine Depletion in Neonatal Cardiomyocytes.Amino Acids 15:135-142 (1998).

20. S.W. Schaffer and M. Mozaffari.The Neonatal STZ Model of Diabetes.IN: J.H. McNeill (Ed.) Experimental Models of Diabetes, CRC Press, Boca Raton, FL, pp. 231-255 (1999).

21. S.W. Schaffer, C. Ballard-Croft, and V. Solodushko. Cardioprotective Effects of Chronic Hyperglycemia: Effect of Hypoxia-Induced Apoptosis and Necrosis. Am. J. Physiol. 278:H1948-H1954 (2000).

22. S.W. Schaffer. J.B. Lombardini, and J. Azuma. Interaction between the Actions of Taurine and Angiotensin II. Amino Acids 18:305-318 (2000).

23. S.W. Schaffer, C. Ballard-Croft, and V. Solodushko. Cardioprotective Effects of Chronic Hyperglycemia: Effect of Hypoxia-Induced Apoptosis and Necrosis. Am. J. Physiol. 278:H1948-H1954 (2000).

24. S.W. Schaffer. J.B. Lombardini, and J. Azuma. Interaction between the Actions of Taurine and Angiotensin II. Amino Acids 18:305-318 (2000).

25. M. Azuma, K. Takahashi, T. Fukuda, Y. Ohyabu, I. Yamamoto, S. Kim, H. Iwao, S.W. Schaffer, and J. Azuma. Taurine Attenuates Hypertrophy Induced by Angiotensin II in Primary Cultured Neonatal Rat Cardiac Myocytes. Eur. J. Pharmacol. 403:181-188 (2000).

26. S.W. Schaffer, K. Takahashi, and J. Azuma. Role of Osmoregulation in the Actions of Taurine. Amino Acids 19:527-546 (2000).

27. K. Takahashi, Y. Ohyabu, S.W. Schaffer, and J. Azuma. Cellular Characterization of an In-Vitro Cell Culture Model of Seal-Induced Cardiac Ischemia. J. Pharm. Pharmacol. 53:379-386 (2001).

28. S. Schaffer. (1) Effect of Hyperglycemia on Myocyte Apoptosis; and (2) Regulation of Apoptosis by Osmotic Stress. Int. Symp., Heart Res., Banff, Alberto, Canada (2001).

29. S. Schaffer. (1) Osmotic Preconditioning through Taurine Depletion and Treatment; (2) Protein Kinase C Distribution: Mechanism Underlying the Interaction Between Taurine and Angiotensin II; and (3) Adverse Effects of Taurine Depletion. 7th Int. Cong., Amino Acids, Vienna, Austria (2001).

30. S. Schaffer. Mechanisms Underlying Taurine-Dependent Heart Failure. 8th World Cong., Clinical Nutrition, Phitsanulok, Thailand (2000).

31. 35. S.W. Schaffer, V. Solodushko and D. Kakhniashvili. Beneficial Effect of Taurine Depletion on Osmotic, Sodium and Calcium Loading. Am. J. Physiol. 282:C1113-1120 (2002).

32. M. Mozaffari and S.W. Schaffer. Chronic Taurine Treatment Ameliorates Reduction in Saline Volume-Induced Diuresis and Natriuresis. Kidney Int. 61:1750-1759 (2002).

33. M. Mozaffari and S.W. Schaffer. Impaired Saline-Stimulated Diuresis and Natriuresis in the Conscious Hypertensive-Glucose Intolerant Rat. Am. J. Hypertension 15:58-65 (2002).

34. S.W. Schaffer and M. Mozaffari. Regulation of Myocardial Phospholipid N-Methylation by Insulin and Diabetes. IN: A. Angel, N. Dhalla, G. Pierce and P. Singal (Eds.) Diabetes and Cardiovascular Disease: Etiology, Treatment and Outcomes. Kluwer Academic/Plenum Publishers, New York, NY, pp. 175-181 (2001).