nach oben

Acta Diabetologica

Erschienen in:

01.12.2010 | Original Article

Breviscapine ameliorates cardiac dysfunction and regulates the myocardial Ca²⁺-cycling proteins in streptozotocin-induced diabetic rats

verfasst von: Min Wang, Wen-bin Zhang, Jun-hui Zhu, Guo-sheng Fu, Bin-quan Zhou

Erschienen in: Acta Diabetologica | Sonderheft 1/2010

Einloggen, um Zugang zu erhalten

Abstract

To investigate the influence of breviscapine on the cardiac structure and function in diabetic cardiomyopathy rats as well as the expression of protein kinase C (PKC) and Ca²⁺-cycling proteins expression. Diabetes was induced in male Sprague–Dawley rats by a single intraperitoneal injection of streptozotocin and the control rats were injected with saline. After the induction of diabetes for 4 weeks, the animals were divided into different groups: (1) normal rats as control; (2) diabetic rats; (3) diabetic rats with administration of breviscapine (10 or 25 mg kg⁻¹ day⁻²). After treatment with breviscapine for 6 weeks, the invasive cardiac function and echocardiographic parameters were measured, and heart tissue was obtained for electron microscope study. The expression of protein kinase C (PKC) and calcium handling regulators, such as protein phosphatase inhibitor-1 (PPI-1), phospholamban (PLB) and Ca²⁺-ATPase (SERCA-2), ryanodine receptor (RyR) were detected by western blot or RT-PCR. The activity of SERCA-2 was measured using Ca²⁺-ATPase kit. Diabetic rats showed impaired cardiac structure and function compared with control rats. The expression of PKC, PLB increased significantly, while the PPI-1, SERCA-2 and RyR expression decreased. Treatment with breviscapine could reverse the cardiac dysfunction and structure changes in diabetic cardiomyopathy rats, and decrease the expression of PKC and PLB, as well as increase the expression of PPI-1, SERCA-2 and RyR. The protective effect of breviscapine was dose related. This study showed that breviscapine could regulate the expression of PKC, PPI-1, PLB and SERCA-2 and have protective effect on diabetic cardiomyopathy.

Wild S, Roglic G, Green A, Sicree R, King H (2004) Global prevalence of diabetes: estimates for the year 2000, projections for 2030. Diabetes Care 27(5):1047–1053CrossRefPubMed

Boudina S, Abel ED (2007) Diabetic cardiomyopathy revisited. Circulation 115(25):3213–3223CrossRefPubMed

Naruse K, King GL (2000) Protein kinase C and myocardial biology and function. Circ Res 86(11):1104–1106PubMed

Okumura K, Akiyama N, Hashimoto H, Ogawa K, Satake T (1988) Alteration of 1, 2-diacylglycerol content in myocardium from diabetic rats. Diabetes 37(9):1168–1172CrossRefPubMed

Brownlee M (2005) The pathobiology of diabetic complications: a unifying mechanism. Diabetes 54(6):1615–1625CrossRefPubMed

Wold LE, Dutta K, Mason MM, Ren J, Cala SE, Schwanke ML, Davidoff AJ, CA SER (2005) Impaired SERCA function contributes to cardiomyocyte dysfunction in insulin resistant rats. J Mol Cell Cardiol 39(2):297–307CrossRefPubMed

Idris I, Gray S, Donnelly R (2001) Protein kinase C activation: isozyme-specific effects on metabolism and cardiovascular complications in diabetes. Diabetologia 44(6):659–673CrossRefPubMed

Zhou W, Wang XL, Lamping KG, Lee HC (2006) Inhibition of protein kinase C beta protects against diabetes-induced impairment in arachidonic acid dilation of small coronary arteries. J Pharmacol Exp Ther 319(1):199–207CrossRefPubMed

Yousif MH (2006) Role of protein kinases in mediating diabetes-induced augmented vasoconstriction to endothelin-1 in the renal arteries of STZ-diabetic rats. Cell Biochem Funct 24(5):397–405CrossRefPubMed

10.

Devereux RB, Roman MJ, Paranicas M, O’Grady MJ, Lee ET, Welty TK, Fabsitz RR, Robbins D, Rhoades ER, Howard BV (2000) Impact of diabetes on cardiac structure and function: the strong heart study. Circulation 101(19):2271–2276PubMed

11.

Way KJ, Katai N, King GL (2001) Protein kinase C and the development of diabetic vascular complications. Diabet Med 18(12):945–959CrossRefPubMed

12.

Gutterman DD (2000) Vascular dysfunction in hyperglycemia: is protein kinase C the culprit? Circ Res 9(1):5–7

13.

Johnsen DD, Kacimi R, Anderson BE, Thomas TA, Said S, Gerdes AM (2005) Protein kinase C isozymes in hypertension and hypertrophy: insight from SHHF rat hearts. Mol Cell Biochem 270(1–2):63–69CrossRefPubMed

14.

Braun M, Simonis G, Birkner K, Pauke B, Strasser RH (2003) Regulation of protein kinase C isozyme and calcineurin expression in isoproterenol induced cardiac hypertrophy. J Cardiovasc Pharmacol 41(6):946–954CrossRefPubMed

15.

Koide Y, Tamura K, Suzuki A, Kitamura K, Yokoyama K, Hashimoto T, Hirawa N, Kihara M, Ohno S, Umemura S (2003) Differential induction of protein kinase C isoforms at the cardiac hypertrophy stage and congestive heart failure stage in Dahl salt-sensitive rats. Hypertens Res 26(5):421–426CrossRefPubMed

16.

Guo M, Wu MH, Korompai F, Yuan SY (2003) Upregulation of PKC genes and isozymes in cardiovascular tissues during early stages of experimental diabetes. Physiol Genomics 12(2):139–146PubMed

17.

Vasanji Z, Cantor EJ, Juric D, Moyen M, Netticadan T (2006) Alterations in cardiac contractile performance and sarcoplasmic reticulum function in sucrose-fed rats is associated with insulin resistance. Am J Physiol Cell Physiol 291(4):C772–C780CrossRefPubMed

18.

Belke DD, Swanson EA, Dillmann WH (2004) Decreased sarcoplasmic reticulum activity and contractility in diabetic db/db mouse heart. Diabetes 53(12):3201–3208CrossRefPubMed

19.

Sakata S, Lebeche D, Sakata Y, Sakata N, Chemaly ER, Liang L, Nakajima-Takenaka C, Tsuji T, Konishi N, del Monte F, Hajjar RJ, Takaki M (2007) Transcoronary gene transfer of SERCA2a increases coronary blood flow and decreases cardiomyocyte size in a type 2 diabetic rat model. Am J Physiol Heart Circ Physiol 292(2):H1204–H1207CrossRefPubMed

20.

Hambleton M, Hahn H, Pleger ST, Kuhn MC, Klevitsky R, Carr AN, Kimball TF, Hewett TE, Dorn GW 2nd, Koch WJ, Molkentin JD (2006) Pharmacological- and gene therapy-based inhibition of protein kinase C alpha/beta enhances cardiac contractility and attenuates heart failure. Circulation 114(6):574–582CrossRefPubMed

21.

Zhou H, Chen S, Wang L, He Q, Fan X (2002) Regulation of the expression of pulmonary arterial collagen by protein kinase C and breviscapine in chronic hypoxic rats. Zhonghua Jie He He Hu Xi Za Zhi 25(6):347–351PubMed

22.

Chen XJ, Cheng DY, Yang L, Xia XQ, Guan J (2006) Effect of breviscapine on fractalkine expression in chronic hypoxic rats. Chin Med J (Engl) 119(17):1465–1468

23.

Zhang SJ, Song Y, Zhai WL, Shi JH, Feng LS, Zhao YF, Chen S (2007) Breviscapine alleviates hepatic injury and inhibits PKC-mRNA and its protein expression in brain-dead BA-Ma mini pigs. Hepatobiliary Pancreat Dis Int 6(6):604–609PubMed

24.

Beckman JA, Goldfine AB, Gordon MB, Garrett LA, Creager MA (2002) Inhibition of protein kinase C beta prevents impaired endothelium-dependent vasodilation caused by hyperglycaemia in humans. Circ Res 90(1):107–111CrossRefPubMed

25.

Braz JC, Gregory K, Pathak A, Zhao W, Sahin B, Klevitsky R, Kimball TF, Lorenz JN, Nairn AC, Liggett SB, Bodi I, Wang S, Schwartz A, Lakatta EG, DePaoli-Roach AA, Robbins J, Hewett TE, Bibb JA, Westfall MV, Kranias EG, Molkentin JD (2004) PKC-alpha regulates cardiac contractility and propensity toward heart failure. Nat Med 10(3):248–254CrossRefPubMed

26.

Hahn HS, Marreez Y, Odley A, Sterbling A, Yussman MG, Hilty KC, Bodi I, Liggrtt SB, Schwartz A, Dorn GW 2nd (2003) Protein kinase C alpha negatively regulates systolic and diastolic function in pathological hypertrophy. Circ Res 93(11):1111–1119CrossRefPubMed

27.

Farese RV, Sajan MP, Standaert ML (2005) Atypical protein kinase C in insulin action and insulin resistance. Biochem Soc Trans 33(Pt 2):350–353PubMed

28.

Das Evcimen N, King GL (2007) The role of protein kinase C activation and the vascular complications of diabetes. Pharmacol Res 55(6):498–510CrossRefPubMed

29.

Pathak A, del Monte F, Zhao W, Schultz JE, Lorenz JN, Bodi I, Weiser D, Hahn H, Carr AN, Syed F, Mavila N, Jha L, Qian J, Marreez Y, Chen G, McGraw DW, Heist EK, Guerrero JL, DePaoli-Roach AA, Hajjar RJ, Kranias EG (2005) Enhancement of cardiac function and suppression of heart failure progression by inhibition of protein phosphatase 1. Circ Res 96(7):756–766CrossRefPubMed

30.

Rodriguez P, Mitton B, Waggoner JR, Kranias EG (2006) Identification of a novel phosphorylation site in protein phosphatase inhibitor-1 as a negative regulator of cardiac function. J Biol Chem 281(50):38599–38608CrossRefPubMed

31.

Sahin B, Shu H, Fernandez J, El-Armouche A, Molkentin JD, Nairn AC, Bibb JA (2006) Phosphorylation of protein phosphatase inhibitor-1 by protein kinase C. J Biol Chem 281(34):24322–24335CrossRefPubMed

32.

Li XL, Li YQ, Yan WM, Li HY, Xu H, Zheng XX, Guo DW, Tang LK (2004) A study of the cardioprotective effect of breviscapine during hypoxia of cardiomyocytes. Planta Med 70(11):1039–1044CrossRefPubMed

33.

Xiong Z, Liu C, Wang F, Li C, Wang W, Wang J, Chen J (2006) Protective effects of breviscapine on ischemic vascular dementia in rats. Biol Pharm Bull 29(9):1880–1885CrossRefPubMed

34.

Lin LL, Liu AJ, Liu JG, Yu XH, Qin LP, Su DF (2007) Protective effects of scutellarin and breviscapine on brain and heart ischemia in rats. J Cardiovasc Pharmacol 50(3):327–332CrossRefPubMed

35.

Liu XD, Chen YZ (2004) The effects of breviscapine on cardiac myocyte apoptosis and expression of Bcl-2 during myocardial ischemia/reperfusion course in rats. J GuiYang Med Coll 29(2):102–104

36.

Li FQ, Chen YZ (2002) Effects of scutellarein on cardiomyocyte apoptosis and ventricular remodeling in spontaneously hypertensive rats. J Chongqing Med Univ 27(4):400–402

37.

Wu YG, Wu GH, Qi XM, Lin H, Qian H, Shen JJ, Lin S (2006) Protein kinase C beta inhibitor LY333531 attenuates intercellular adhesion molecule-1 and monocyte chemotactic protein-1 expression in the kidney in diabetic rats. J Pharmacol Sci 101(4):335–343CrossRefPubMed

38.

Cotter MA, Jack AM, Cameron NE (2002) Effects of the protein kinase C beta inhibitor LY333531 on neural and vascular function in rats with streptozotocin -induced diabetes. Clin Sci (Lond) 103(3):311–321

Titel: Breviscapine ameliorates cardiac dysfunction and regulates the myocardial Ca2+-cycling proteins in streptozotocin-induced diabetic rats
verfasst von: Min Wang
Wen-bin Zhang
Jun-hui Zhu
Guo-sheng Fu
Bin-quan Zhou
Publikationsdatum: 01.12.2010
Verlag: Springer Milan
Erschienen in: Acta Diabetologica / Ausgabe Sonderheft 1/2010
Print ISSN: 0940-5429
Elektronische ISSN: 1432-5233
DOI: https://doi.org/10.1007/s00592-009-0164-x

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Sonderheft 1/2010

Effect of pioglitazone on systemic inflammation is independent of metabolic control and cardiac autonomic function in patients with type 2 diabetes

Excessive maternal transmission of diabetes in Japanese families with young-onset type 2 diabetes and insulin secretion defect according to clinical features

The oxidative stress status in diabetes mellitus and diabetic nephropathy

How increased VEGF induces glomerular hyperpermeability: a potential signaling pathway of Rac1 activation

Diabetes and the risk of sudden cardiac death, the Atherosclerosis Risk in Communities study