Lack of both oxygen and glucose contributes to I/R-induced changes in cardiac SR function.

نویسندگان

  • Rana M Temsah
  • Thomas Netticadan
  • Ken-Ichi Kawabata
  • Naranjan S Dhalla
چکیده

Although ischemia-reperfusion (I/R) has been shown to depress cardiac performance and sarcoplasmic reticulum (SR) function, the mechanisms underlying these alterations are poorly understood. Because lack of oxygen and substrate deprivation are known to occur during the ischemic phase, we examined the effects of reperfusion on cardiac performance and SR function in hearts subjected to hypoxia and substrate lack. For this purpose, isolated rat hearts were perfused with hypoxic and/or glucose-free medium for 30 min and then reperfused with normal medium for 1 h; the SR vesicles were isolated for studying the Ca(2+)-transport activities. Reperfusion with normal medium of hearts deprived of oxygen or glucose showed no changes in cardiac performance and SR function. However, reperfusion of hearts perfused with hypoxic glucose-free medium showed ~45% decrease in cardiac contractile activities as well as 23 and 64% reduction in SR Ca(2+)-uptake and Ca(2+)-release activities, respectively, without any change in the level of SR Ca(2+)-cycling proteins. Depressed SR function in these hearts was associated with a reduction in Ca(2+)/calmodulin-dependent protein kinase (CaMK) phosphorylation of the SR Ca(2+)-cycling proteins and 34% decrease in SR CaMK activity. These changes in cardiac performance, SR function, and SR CaMK activity in the hypoxic, glucose-deprived, reperfused hearts were similar to those observed in hearts subjected to 30 min of global ischemia and 60 min of reperfusion. The results therefore suggest that the lack of both oxygen and substrate during the ischemic phase may contribute to the I/R-induced alterations in cardiac performance and SR function. Furthermore, these abnormalities were associated with reduced SR CaMK activity.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Pioglitazone alleviates oxygen and glucose deprivation-induced injury by up-regulation of miR-454 in H9c2 cells

Objective(s): Pioglitazone, an anti-diabetic agent, has been widely used to treat type II diabetes. However, the effect of pioglitazone on myocardial ischemia reperfusion injury (MIRI) is still unclear. Herein, the objective of this study is to learn about the regulation and mechanism of pioglitazone effects on oxygen glucose deprivation (OGD)-induced myocardial cell injury.Materials and Method...

متن کامل

Aqueous extract of Berberis integerrima root improves renal dysfunction in streptozotocin induced diabetic rats

Objective: Barberry root extract contains various alkaloids that are considered as antioxidants. Beneficial effect of aqueous extract of Berberis integerrima root (AEBIR) was evaluated for renal function in diabetic rats induced by STZ. Material and Methods: Diabetes was induced by i.p. injection of streptozotocin (65 mg/kg bw) to rats, after 15 h of fasting. Diabetic rats were randomly grouped...

متن کامل

The Effect of Noscapine on Oxygen-Glucose Deprivation on Primary Murine Cortical Neurons in High Glucose Condition

AbstractIn the present work we set out to investigate the neuroprotective effects of noscapine (0.5-2 µM) in presence of D-glucose on primary murine foetal cortical neurons after oxygen–glucose deprivation/24 hrs recovery. Cell viability, nitric oxide production and intracellular calcium ([ca2+]i) levels were evaluated by MTT assay, the modified Griess method and Fura-2 respectively. 25 and 100...

متن کامل

The Effect of Noscapine on Oxygen-Glucose Deprivation on Primary Murine Cortical Neurons in High Glucose Condition

AbstractIn the present work we set out to investigate the neuroprotective effects of noscapine (0.5-2 µM) in presence of D-glucose on primary murine foetal cortical neurons after oxygen–glucose deprivation/24 hrs recovery. Cell viability, nitric oxide production and intracellular calcium ([ca2+]i) levels were evaluated by MTT assay, the modified Griess method and Fura-2 respectively. 25 and 100...

متن کامل

Preconditioning prevents alterations in cardiac SR gene expression due to ischemia-reperfusion.

We have previously shown that ischemic preconditioning (IP) improves cardiac performance and sarcoplasmic reticulum (SR) function in hearts subjected to ischemia-reperfusion (I/R). In this study, we examined the effect of IP on I/R-induced changes in gene expression for SR proteins such as the Ca(2+) release channel, Ca(2+) pump ATPase, phospholamban, and calsequestrin in the isolated rat heart...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • American journal of physiology. Cell physiology

دوره 283 4  شماره 

صفحات  -

تاریخ انتشار 2002