Hypoxia can cause basement membrane (BM) degradation in tissues. Matrix metalloproteinase 9 (MMP-9) is involved in various human cancers as well as BM degradation by downregulating type IV collagen (COL4). This study investigated the role of MMP-9 in hypoxia-mediated BM degradation in rat bone marrow based on its regulation of collagen type IV alpha 1 chain (COL4A1). Eighty male rats were randomly divided into four groups based on exposure to hypoxic conditions at a simulated altitude of 7,000 m, control (normoxia) and 3, 7, and 10 days of hypoxia exposure. BM degradation in bone marrow was determined by transmission electron microscopy. MMP-9 levels were assessed by western blot and real-time PCR, and COL4A1 levels were assessed by western blot and immunohistochemistry. Microvessels BMs in bone marrow exposed to acute hypoxia were observed by electron microscopy. MMP-9 expression increased, COL4A1 protein expression decreased, and BM degradation occurred in the 10-, 7-, and 3-day hypoxia groups compared with that in the control group (all P < 0.05). Hypoxia increased MMP-9 levels, which in turn downregulated COL4A1, thereby increasing BM degradation. MMP-9 upregulation significantly promoted BM degradation and COL4A1 downregulation. Our results suggest that MMP-9 is related to acute hypoxia-induced BM degradation in bone marrow by regulating COL4A1.

• MeSH
• Basement Membrane * metabolism   MeSH
• Hypoxia metabolism   MeSH
• Collagen Type IV * metabolism   MeSH
• Rats MeSH
• Matrix Metalloproteinase 9 * metabolism   MeSH
• Up-Regulation MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Collagen Type IV * MeSH
• Matrix Metalloproteinase 9 * MeSH
• Mmp9 protein, rat MeSH Browser

Antifreeze proteins are an effective additive for low-temperature preservation of solid organs. Here, we compared static hypothermic preservation with and without antifreeze glycoprotein (AFGP), followed by nonfreezing cryopreservation of rat hearts. The heart was surgically extracted and immersed in one of the cardioplegia solutions after cardiac arrest. Control rat hearts (n=6) were immersed in University of Wisconsin (UW) solution whereas AFGP-treated hearts (AFGP group) (n=6) were immersed in UW solution containing 500 ?g/ml AFGP. After static hypothermic preservation, a Langendorff apparatus was used to reperfuse the coronary arteries with oxygenated Krebs-Henseleit solution. After 30, 60, 90, and 120 min, the heart rate (HR), coronary flow (CF), cardiac contractile force (max dP/dt), and cardiac diastolic force (min dP/dt) were measured. Tissue water content (TWC) and tissue adenosine triphosphate (ATP) levels in the reperfused preserved hearts were also assessed. All the parameters were compared between the control and AFGP groups. Compared with the control group, the AFGP group had significantly (p<0.05) higher values of the following parameters: HR at 60, 90, and 120 min; CF at all four time points; max dP/dt at 90 min; min dP/dt at 90 and 120 min; and tissue ATP levels at 120 min. TWC did not differ significantly between the groups. The higher HR, CF, max dP/dt, min dP/dt, and tissue ATP levels in the AFGP compared with those in control hearts suggested that AFGP conferred superior hemodynamic and metabolic functions. Thus, AFGP might be a useful additive for the static/nonfreezing hypothermic preservation of hearts.

• MeSH
• Adenosine Triphosphate metabolism   MeSH
• Cardioplegic Solutions pharmacology   MeSH
• Cryopreservation methods   MeSH
• Antifreeze Proteins pharmacology   MeSH
• Rats MeSH
• Models, Animal MeSH
• Rats, Wistar MeSH
• Heart * MeSH
• Transplants supply & distribution   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Adenosine Triphosphate MeSH
• Cardioplegic Solutions MeSH
• Antifreeze Proteins MeSH

The purpose of this review is to analyze the involvement of protein kinases in the cardioprotective mechanism induced by chronic hypoxia. It has been reported that chronic intermittent hypoxia contributes to increased expression of the following kinases in the myocardium: PKCdelta, PKCalpha, p-PKCepsilon, p-PKCalpha, AMPK, p-AMPK, CaMKII, p-ERK1/2, p-Akt, PI3-kinase, p-p38, HK-1, and HK-2; whereas, chronic normobaric hypoxia promotes increased expression of the following kinases in the myocardium: PKCepsilon, PKCbetaII, PKCeta, CaMKII, p-ERK1/2, p-Akt, p-p38, HK-1, and HK-2. However, CNH does not promote enhanced expression of the AMPK and JNK kinases. Adaptation to hypoxia enhances HK-2 association with mitochondria and causes translocation of PKCdelta, PKCbetaII, and PKCeta to the mitochondria. It has been shown that PKCdelta, PKCepsilon, ERK1/2, and MEK1/2 are involved in the cardioprotective effect of chronic hypoxia. The role of other kinases in the cardioprotective effect of adaptation to hypoxia requires further research.

• MeSH
• Chronic Disease MeSH
• Hypoxia enzymology   MeSH
• Cardiotonic Agents pharmacology   MeSH
• Humans MeSH
• Heart Diseases enzymology   etiology   prevention & control   MeSH
• Protein Kinases metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Cardiotonic Agents MeSH
• Protein Kinases MeSH